AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER
Dec 292017
 

 

Green Chem., 2018, Advance Article
DOI: 10.1039/C7GC02627G, Paper
Kathiravan Murugesan, Thirusangumurugan Senthamarai, Manzar Sohail, Muhammad Sharif, Narayana V. Kalevaru, Rajenahally V. Jagadeesh
Nanoscale Fe2O3-catalyzed environmentally benign synthesis of nitriles and amides has been performed from easily accessible aldehydes and ammonia using O2.

Stable and reusable nanoscale Fe2O3-catalyzed aerobic oxidation process for the selective synthesis of nitriles and primary amides

Author affiliations

Abstract

The sustainable introduction of nitrogen moieties in the form of nitrile or amide groups in functionalized molecules is of fundamental interest because nitrogen-containing motifs are found in a large number of life science molecules, natural products and materials. Hence, the synthesis and functionalization of nitriles and amides from easily available starting materials using cost-effective catalysts and green reagents is highly desired. In this regard, herein we report the nanoscale iron oxide-catalyzed environmentally benign synthesis of nitriles and primary amides from aldehydes and aqueous ammonia in the presence of 1 bar O2 or air. Under mild reaction conditions, this iron-catalyzed aerobic oxidation process proceeds to synthesise functionalized and structurally diverse aromatic, aliphatic and heterocyclic nitriles. Additionally, applying this iron-based protocol, primary amides have also been prepared in a water medium.

1H NMR (300 MHz, Chloroform-d) δ 7.17 – 6.96 (m, 2H), 6.93 – 6.70 (m, 1H), 4.33 – 4.11 (m, 4H). 13C NMR (75 MHz, Chloroform-d) δ 147.75 , 143.80 , 125.87 , 121.21 , 118.91 , 118.25 , 104.38 , 64.59 , 64.12 . Off white solid

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cas 19102-07-9

  • 1,4-Benzodioxan-6-carbonitrile (8CI)
  • 2,3-Dihydro-1,4-benzodioxin-6-carbonitrile
  • 1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)nitrile

 

MP

Melting Point, °C
105 – 106

Tetrahedron, 2015, vol. 71,  29, p. 4883 – 4887

NMR PREDICTS

1H NMR

 

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13C NMR PREDICT

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More…………….

Journal of the American Chemical Society, 2001, vol. 123, 49, p. 12202 – 12206

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RSC Advances, 2013, vol. 3, 44, p. 22389 – 22396

http://www.rsc.org/suppdata/ra/c3/c3ra44386h/c3ra44386h.pdf

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MORE……..

Organic Letters, 2017, vol. 19,  12, p. 3095 – 3098

http://pubs.acs.org/doi/suppl/10.1021/acs.orglett.7b01199/suppl_file/ol7b01199_si_001.pdf

2,3-Dihydrobenzo[b][1,4]dioxine-6-carbonitrile (Scheme 1, 2n) According to the general procedure A, the reaction of 1n (0.20 mmol), zinc cyanide (2.0 equiv), PCyPh2 (0.20 equiv) and Pd(OAc)2 (0.05 equiv) in dioxane (0.25 M) for 16 h at 150 °C, afforded after work-up and chromatography the title compound in 75% yield (24.2 mg). White solid. 1H NMR (500 MHz, CDCl3) δ 7.17-7.11 (m, 2H), 6.91 (d, J = 8.1 Hz, 1H), 4.32-4.31 (m, 2H), 4.30- 4.26 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 147.84, 143.91, 126.04, 121.37, 119.01, 118.37, 104.62, 64.71, 64.24.

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Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected α-amino acids in water

 organic chemistry, spectroscopy, SYNTHESIS  Comments Off on Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected α-amino acids in water
Dec 202017
 

Green Chem., 2018, Advance Article
DOI: 10.1039/C7GC02862H, Paper
Peter Olsen, Michael Oschmann, Eric V. Johnston, Bjorn Akermark
Ring opening of cyclic carbonates with unprotected amino acids in water – a route to highly functional carbamates.

Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected α-amino acids in water

 Author affiliations

Abstract

The present work shows that it is possible to ring-open cyclic carbonates with unprotected amino acids in water. Fine tuning of the reaction parameters made it possible to suppress the degree of hydrolysis in relation to aminolysis. This enabled the synthesis of functionally dense carbamates containing alkenes, carboxylic acids, alcohols and thiols after short reaction times at room temperature. When Glycine was used as the nucleophile in the ring-opening with four different five membered cyclic carbonates, containing a plethora of functional groups, the corresponding carbamates could be obtained in excellent yields (>90%) without the need for any further purification. Furthermore, the orthogonality of the transformation was explored through ring-opening of divinylenecarbonate with unprotected amino acids equipped with nucleophilic side chains, such as serine and cysteine. In these cases the reaction selectively produced the desired carbamate, in 70 and 50% yield respectively. The synthetic design provides an inexpensive and scalable protocol towards highly functionalized building blocks that are envisioned to find applications in both the small and macromolecular arena.

link  http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C7GC02862H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

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Image result for Peter Olsén stockholm
Affiliation

Stockholm University

Location
  • Stockholm, Sweden
Position
  • PostDoc Position

Research experience

  • Jun 2010–Feb 2016
    PhD Student
    KTH Royal Institute of Technology · Department of Fibre and Polymer Technology
    Sweden · Stockholm
Stockholms universitet hem
Image result for Björn Åkermark stockholm

Education

  • Jan 1962–Jun 1967
    KTH Royal Institute of Technology
    Organic Chemistry and Catalysis · PhD
    Sweden · Stockholm

Awards & achievements

  • Jun 2009

    Award: Bror Holmberg Medal, Swedish Chemical Society

  • Feb 2009

    Award: Ulla and Stig Holmquists Prize, Uppsala University

  • Oct 1997

    Award: Dr hc, University D´Aix-Marseille

  • Oct 1991

    Award: KTH Prize for Excellence in Teaching

  • Oct 1978

    Award: Arrhenius Medal, Swedish Chemical Society

  • Aug 1977

    Scholarship: Zorn Fellowship, Swden America Foundation

  • Nov 1976

    Award: Letterstedt Award, Roy Swed. Acad. of Science

6.jpg

Dr. Eric Johnston, Ph.D.

Sigrid Therapeutics

Chief Technology Officer

Dr. Eric V. Johnston obtained his Master of Science degree in 2008 at the Department of Organic Chemistry, Stockholm University, Sweden. In the same year, he started his graduate studies under the supervision of Prof. Jan-Erling Bäckvall. During his PhD, he worked on the development of new homogeneous and heterogeneous transition-metal catalysts.

After receiving his PhD in 2012, he joined Prof. Samuel J. Danishefskys research group at Memorial Sloan-Kettering Cancer Center, New York, USA as a postdoctoral fellow supported by The Swedish Research Council. Here he was engaged in the total chemical synthesis of glycolsylated proteins that play important roles in modern cancer treatment.

In 2014 he returned to the Department of Organic Chemistry at Stockholm University to establish his own group. The goal of his research is to contribute new advances to the strategy and methodology for the preparation of synthetic macromolecules such as proteins, glycopeptides, sequence and length-controlled polymers. He is also a Co-Supervisor for Prof. Björn Åkermarks research group, which aims at studying and developing new homogeneous, as well as heterogeneous, water oxidation catalysts.

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Transition-Metal-Free Cross-Coupling of Aryl and Heteroaryl Thiols with Arylzinc Reagents

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Transition-Metal-Free Cross-Coupling of Aryl and Heteroaryl Thiols with Arylzinc Reagents
Nov 092017
 

Zhong-Xia WANG

STR1

 

STR1

N,N-dimethyl-4-biphenylamine

Molecular Formula, C14H15N
Molecular Weight, 197.28
CAS Number, 1137-79-7

(1) N,N-dimethyl-[1,1′-biphenyl]-4-amine (3a) 5,6

Elute: EtOAc/petroleum ether: 1/100 (v/v), white solid, yield 97.8 mg (99%).

1H NMR (400 MHz, CDCl3): δ 7.56 (d, J = 7.8 Hz, 2H), 7.51 (d, J = 8.8 Hz, 2H), 7.40 (t, J = 7.7 Hz, 2H), 7.30–7.21 (m, 1H), 6.81 (d, J = 8.8 Hz, 2H), 3.00 (s, 6H).

13C NMR (101 MHz, CDCl3): δ 150.09, 141.34, 129.37, 128.78, 127.84, 126.43, 126.12, 112.90, 40.97.

5 Yang, X.; Wang, Z.-X. Organometallics 2014, 33, 5863.

(6) Stibingerova, I.; Voltrova, S.; Kocova, S.; Lindale, M.; Srogl, J. Org. Lett. 2016, 18, 312.

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Transition-Metal-Free Cross-Coupling of Aryl and Heteroaryl Thiols with Arylzinc Reagents

Bo Yang and Zhong-Xia Wang* 
 CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China
 Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, P. R. China
Org. Lett., Article ASAP
DOI: 10.1021/acs.orglett.7b03145

Abstract

Abstract Image

Cross-coupling of (hetero)arylthiols with arylzinc reagents via C–S cleavage was performed under transition-metal-free conditions. The reaction displays a wide scope of substrates and high functional-group tolerance. Electron-rich and -deficient (hetero)arylthiols and arylzinc reagents can be employed in this transformation. Mg2+ and Li+ ions were demonstrated to facilitate the reaction.

In summary, we developed a transition-metal-free coupling reaction of (hetero)arylthiols with arylzinc reagents to form bi(hetero)aryls. The reaction exhibited wide substrate scope and good compatibility of functional groups. Electron-rich and -poor aryl or heteroaryl thiols can be converted. Various arylzinc reagents, including electron-rich and electron-poor reagents, can be employed as the coupling partners. Preliminary mechanistic studies suggest a nucleophilic aromatic substitution pathway, and Mg2+ and Li+ ions play important roles in the process of reaction. This study provides an example of S2– as a leaving group in an aromatic system and an effective methodology for the synthesis of bi(hetero)aryls including pharmaceutical molecules without transition-metal impurities.

Zhong-Xia WANG

Department: Department of Chemistry
Mailing Address:
Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Rd, Hefei, Anhui, 230026, PR China
Postal Code:
230026
Phone:
+86-551-63603043
Fax:
Homepage:
http://chem.ustc.edu.cn/szdw_16/bd/201210/t20121023_142877.html
Zhong-Xia Wang is a professor in the Department of Chemistry at the University of Science and Technology 
of China. He received his BS degree (1983) and MS degree (1986) from Nankai University, 
and PhD degree (1997) from the University of Sussex, UK. Since July 1986, Wang has been working 
at the University of Science and Technology of China (USTC) successively as Assistant, 
Lecturer, Associate Professor, and Professor. From Aug. 1993 to Oct. 1996, he pursued his doctoral 
studies at the University of Sussex, UK, and from Oct. 1999 to Oct. 2000, he was a Research Associate 
at the Chinese University of Hong Kong.

 学 系
Department of Chemistry

Predicts

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http://pubs.acs.org/doi/10.1021/acs.orglett.7b03145

 

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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An efficient green protocol for the synthesis of tetra-substituted imidazoles catalyzed by zeolite BEA: effect of surface acidity and polarity of zeolite

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on An efficient green protocol for the synthesis of tetra-substituted imidazoles catalyzed by zeolite BEA: effect of surface acidity and polarity of zeolite
Nov 032017
 

Image result for Kalpana C. Maheria sv

1-benzyl-2, 4, 5-triphenyl-1H-imidazole

STR1 STR2 str3

. 1-Benzyl-2,4,5-triphenyl-1H-imidazole (5a, n = 1).

Off-white solid; m.p.: 160–162 °C;

anal. calcd. for C28H22N2: C, 87.01, H, 5.74, N, 7.25%. Found: C, 87.13, H, 5.70, N, 7.19%;

UV (λmax, ethanol) = 280 nm;

FT-IR (KBr, cm−1 ): 3060 (C–H stretch), 3031, 1600 (CN), 1497, 1483, 1447 (CC), 1352 (C–N stretch), 769, 697 (C–H band);

1 H NMR (400 MHz, DMSO): 5.16 (s, 2H, CH2), 6.74–7.67 (m, 20H, Ar–H) ppm;

13C NMR (100 MHz, DMSO): 47.6 (CH2, C8), 125.1 (CHarom, C28), 126.0 (CHarom, C26), 126.2 (CHarom, C30), 126.4 (CHarom, C11), 127.0 (CHarom, C15), 127.1 (CHarom, C16), 127.7 (CHarom, C20), 128.0 (CHarom, C21), 128.1 (CHarom, C25), 128.4 (CHarom, C13), 128.5 (CHarom, C18), 128.6 (CHarom, C27), 128.8 (C1), 128.8 (CHarom, C12), 128.9 (CHarom, C14), 130.1 (CHarom, C17), 130.3 (CHarom, C19), 130.5 (CHarom, C22), 130.7 (CHarom, C24), 131.0 (CHarom, C29), 134.4 (CHarom, C9), 135.1 (CHarom, C23), 136.8 (CHarom, C7), 137.0 (CHarom, C10), 137.2 (CHarom, C6), 145.4 (C2), 147.0 (C4) ppm;

MS: m/z = 387.5 (M + H)+

An efficient green protocol for the synthesis of tetra-substituted imidazoles catalyzed by zeolite BEA: effect of surface acidity and polarity of zeolite

*Corresponding authors

Abstract

In the present study, the catalytic activity of various medium (H-ZSM-5) and large pore (H-BEA, H-Y, H-MOR) zeolites were studied as solid acid catalysts. The zeolite H-BEA is found to be an efficient catalyst for the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles through one-pot, 4-component reaction (4-CR) between benzil, NH4OAc, substituted aromatic aldehydes and benzyl amine. The hydrophobicity, Si/Al ratio and acidic properties of zeolite BEA were well improved by controlled dealumination. The synthesized materials were characterized by various characterization techniques such as XRD, ICP-OES, BET, NH3-TPD, FT-IR, pyridine FT-IR, 27Al and 1H MAS NMR. It has been observed that the dealumination of the parent zeolite H-BEA (12) results in the enhanced strength of Brønsted acidity up to a certain Si/Al ratio which is attributed to the inductive effect of Lewis acidic EFAl species, leading to the higher activity of the zeolite BEA (15) catalyst towards the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles under thermal solvent-free conditions with good to excellent yields. Using the present catalytic synthetic protocol, diverse tetra-substituted imidazoles, which are among the significant biologically active scaffolds, were synthesized in high yield within a shorter reaction time. The effect of polarity, surface acidity and extra framework Al species of the catalysts has been well demonstrated by means of pyridine FT-IR, and 27Al and 1H MAS NMR. The solvent-free synthetic protocol makes the process environmentally benign and economically viable.

Graphical abstract: An efficient green protocol for the synthesis of tetra-substituted imidazoles catalyzed by zeolite BEA: effect of surface acidity and polarity of zeolite
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Image result for S. V. National Institute of Technology, Ichchhanath, Surat
Image result for S. V. National Institute of Technology, Ichchhanath, Surat
Image result for S. V. National Institute of Technology, Ichchhanath, Surat
S. V. National Institute of Technology, Ichchhanath, Surat
Image result for Mandvi Science College, Mandvi – 394160, Surat, India
Image result for Mandvi Science College, Mandvi – 394160, Surat, India
Mandvi Science College, Mandvi – 394160, Surat, India

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DISCLAIMER

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent
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Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile

 spectroscopy, SYNTHESIS  Comments Off on Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile
Apr 222017
 

Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile

 Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC00602K, Communication
Katharina J. Hock, Robin Spitzner, Rene M. Koenigs
Applications of diazo acetonitrile in cyclopropa(e)nation reactions are realized in a slow-release protocol with bench-stable reagents. Cyclopropyl nitriles are obtained in one step in good diastereoselectivity on a gram-scale providing an efficient entry into this class of fragrances and drug-like molecules.
STR1
STR2
trans-2-phenylcyclopropane-1-carbonitrile
colorless solid (46 mg, 81%);
m.p. = 29°C;
1 H-NMR (600 MHz, CDCl3): δ = 7.34 – 7.30 (m, 2H), 7.28 – 7.24 (m, 1H), 7.12 – 7.08 (m, 2H), 2.63 (ddd, J = 9.2, 6.7, 4.7 Hz, 1H), 1.62 (dt, J = 9.2, 5.4 Hz, 1H), 1.55 (ddd, J = 8.7, 5.5, 4.8 Hz, 1H), 1.45 (ddd, J = 8.8, 6.7, 5.3 Hz, 1H);
13C-NMR (151 MHz, CDCl3): δ = 137.55, 128.76, 127.41, 126.31, 121.05, 24.90, 15.24, 6.63;
HRMS (ESI): m/z calc. for [C10H9NNa]: 166.06272, found 166.06276;
IR (KBr): νmax/cm-1 = 3044, 2235, 2098, 1761, 1600, 1461, 1220, 1051, 920, 705.
The analytical data is in correspondence with the literature [2]
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[2] M. Gao, N. N. Patwardhan, P. R. Carlier, J. Am. Chem. Soc., 2013, 135 (38), 14390–14400

Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile

Author affiliations

Abstract

Diazo acetonitrile has long been neglected despite its high value in organic synthesis due to a high risk of explosions. Herein, we report our efforts towards the transient and safe generation of this diazo compound, its applications in iron catalyzed cyclopropanation and cyclopropenation reactions and the gram-scale synthesis of cyclopropyl nitriles.

Graphical abstract: Towards nitrile-substituted cyclopropanes – a slow-release protocol for safe and scalable applications of diazo acetonitrile
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(3R)-4-[2-chloro-6-[[(R)-methylsulfinyl]methyl]pyrimidin-4-yl]-3-methyl-morpholine

 spectroscopy  Comments Off on (3R)-4-[2-chloro-6-[[(R)-methylsulfinyl]methyl]pyrimidin-4-yl]-3-methyl-morpholine
Feb 092017
 

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(3R)-4-[2-chloro-6-[[(R)-methylsulfinyl]methyl]pyrimidin-4-yl]-3-methyl-morpholine

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Synthesis of (3R)-4-[2-chloro-6-[[(R)-methylsulfinyl]methyl]pyrimidin-4-yl]-3-methyl-morpholine (10)

off-white solid (53.9 kg, 68.3% yield). 1H NMR (400 MHz, DMSO-d6, δ): 1.20 (d, J = 6.8 Hz, 3 H), 2.52 (m, 1 H), 2.63 (s, 3 H), 3.21 (m, 1 H), 3.44 (m, 1 H), 3.58 (dd, J = 11.6, 3.1 Hz, 1 H), 3.72 (d, J = 11.5 Hz, 1 H), 3.92 (m, 3 H), 4.07 (d, J = 12.4 Hz, 1 H), 6.80 (s, 1 H); Assay (HPLC) 99%; Assay (QNMR) 100%; Chiral purity (HPLC) (R,R)-diastereoisomer 99.6%, (R,S)-diastereoisomer 0.4%.

 

Abstract Image

A Baeyer–Villiger monooxygenase enzyme has been used to manufacture a chiral sulfoxide drug intermediate on a kilogram scale. This paper describes the evolution of the biocatalytic manufacturing process from the initial enzyme screen, development of a kilo lab process, to further optimization for plant scale manufacture. Efficient gas–liquid mass transfer of oxygen is key to obtaining a high yield.

Development and Scale-up of a Biocatalytic Process To Form a Chiral Sulfoxide

The Departments of Pharmaceutical Sciences and Pharmaceutical Technology and Development, AstraZeneca, Silk Road Business Park, Macclesfield, Cheshire SK10 2NA, United Kingdom
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00391
Publication Date (Web): January 4, 2017
Copyright © 2017 American Chemical Society
*Tel: +44 (0)1625-519149. E-mail: william.goundry@astrazeneca.com.
Figure
Examples of biologically active molecules containing a sulfoxide or sulfoximine: esomeprazole (3), aprikalim (4), oxisurane (5), OPC-29030 (6), ZD3638 (7), buthionine sulfoximine (8), and AZD6738 (9).

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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(±)-trans-ethyl 2-(3,4-difluorophenyl)Cyclopropanecarboxylate

 spectroscopy  Comments Off on (±)-trans-ethyl 2-(3,4-difluorophenyl)Cyclopropanecarboxylate
Feb 092017
 

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(±)-trans-ethyl 2-(3,4-difluorophenyl)Cyclopropanecarboxylate

C12H12F2O2

GC-MS (EI) m/z: [M]+ calc. for C12H12F2O2 + : 226.08; found: 226.08.

δH (400 MHz, CDCl3): 1.25 (1H, ddd, 3 J 8.4 Hz, 3 J 6.4 Hz, 2 J 4.5 Hz , 3-H); 1.28 (3H, t 3 J 6.4 Hz CH3Ethyl) 1.57-1.62 (2H, m, 3 J 9.2 Hz, 3 J 5.2 Hz, 2 J 4.5 Hz, 3-H + H2O), 1.84 (1H, ddd, 3 J 8.5 Hz, 3 J 5.3 Hz, 3 J 4.3 Hz , 2-H), 2.47 (1H, ddd, 3 J 9.5 Hz, 3 J 6.4 Hz, 3 J 4.2 Hz , 1-H), 4.17 (2H, q, 3 J 6.3 Hz, CH2Ethyl) 6.81-6.87 (1H, m, 3 J 8.5 Hz, 4 J 7.6 Hz, 4 J 2.4 Hz, 6-H’ ), 6.88 (1H, ddd, 3 J 11.5 Hz, 4 J 7.6 Hz, 4 J 2.2 Hz, 2-H’) 7.06 (1H, dt, 3 J 10.3 Hz, 3 J 8.2 Hz. 5-H’).

δc (400 MHz, CDCl3): 14.27 (CH3Ethyl), 16.84 (3-C) 24.04 (1-C), 25.14 (d, 4 J 1.4, 2-C), 60.71 (CH2Ethyl), 114.74 (d, 2 J 19 Hz, 2-C’), 117.09 (d, 2 J 18 Hz, 5-C’), 122.25 (dd, 3 J 6.1 Hz, 4 J 3.4 Hz, 6- C’), 137.06 (dd, 3 J 6.1 Hz, 4 J 3.4 Hz, 1- C’), 149.2 (dd, 1 J 248 Hz, 2 J 13 Hz, 4-C’) 151.32 (dd, 1 J 249 Hz, 2 J 12.5 Hz, 3-C’) 172.87 (Ccarbonyl).

[ ] 20 a D = -381.9 (c 1.0 in EtOH) for (1R,2R)-3, ee = 95%

Abstract Image

In this study a batch reactor process is compared to a flow chemistry approach for lipase-catalyzed resolution of the cyclopropanecarboxylate ester (±)-3. (1R,2R)-3 is a precursor of the amine (1R,2S)-2 which is a key building block of the API ticagrelor. For both flow and batch operation, the biocatalyst could be recycled several times, whereas in the case of the flow process the reaction time was significantly reduced.

Comparison of a Batch and Flow Approach for the Lipase-Catalyzed Resolution of a Cyclopropanecarboxylate Ester, A Key Building Block for the Synthesis of Ticagrelor

School of Chemistry, University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, Manchester M1 7DN, United Kingdom
Chemessentia, SRL – Via G. Bovio, 6-28100 Novara, Italy
§ Institute of Process Research and Development, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, United Kingdom
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00346
Publication Date (Web): December 22, 2016
Copyright © 2016 American Chemical Society

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on 2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid
Feb 012017
 

 

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2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid

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2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid 

as a white solid. Mp: 162–163 °C, % purity: 94.09% (HPLC);
1H NMR (DMSO-d6, 400 MHz) δ: 1.38 (s, 9H), 2.10–2.18 (m, 2H), 2.28–2.32 (m, 2H), 2.49–2.50 (m, 2H, merged with DMSO peak), 2.97–3.03 (m, 2H), 3.33–3.40 (m, 2H), 12.23 (bs, 2H); 1H NMR (CD3OD, 400 MHz) δ: 1.46 (s, 9H), 2.26 (ddd, J1 = 2.8 Hz, J2 = 9.2 Hz, J3 = 16.0 Hz, 2H), 2.43 (dd, J1 = 5.2 Hz, J2 = 16.0 Hz, 2H), 2.69 (m, 2H), 3.16 (dd, J1 = 5.2 Hz, J2 = 10.8 Hz, 2H), 3.49–3.54 (m, 2H);
13C NMR (DMSO-d6, 100 MHz) δ: 28.49, 32.97, 36.49, 37.31, 50.10, 50.20, 78.67, 154.05, 173.96;
IR (KBr): ν = 871, 933, 1143, 1166, 1292, 1411, 1689, 1708, 2881, 2929, 2980, 3001 cm–1;
TOFMS: [C13H21NO6 – H+]: calculated 286.1296, found 286.1031(100%).
HPLC conditions were as follows for compound ; Agilent 1100 series, column: YMC J’SPHERE C18 (150 mm X 4.6 mm) 4µm with mobile phases A (0.05% TFA in water) and B (acetonitrile). Detection was at 210 nm, flow was set at 1.0 mL/min, and the temperature was 30 °C (Run time: 45 min). Gradient: 0 min, A = 90%, B = 10%; 5.0 min, A = 90%, B = 10%; 25 min, A = 0%, B = 100%; 30 min, A = 0%, B = 100%, 35 min, A = 90%, B = 10%; 45 min, A = 90%, B = 10%.
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00399
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Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate)

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate)
Jan 312017
 

str5

Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate)

STR1

IR (CHCl3): ν = 758, 1215, 1278, 1437, 1660, 1720, 2806, 2953, 3020, 3421 cm–1;

 

STR2

13C NMR (CDCl3, 100 MHz) δ: 51.53, 53.42, 58.37, 122.66, 127.28, 128.41, 128.55, 128.76, 138.24, 145.84, 166.58;

 

STR3

1H NMR (CDCl3, 400 MHz) δ: 3.23 (dd, J1 = 1.6 Hz, J2 = 6.0 Hz, 4H), 3.62 (s, 2H), 3.75 (s, 6H), 6.07 (dt, J1 = 1.6 Hz, J2 = 16.0 Hz, 2H), 6.97 (dt, J1 = 6.0 Hz, J2 = 16.0 Hz, 2H), 7.25–7.34 (m, 5H-merged with CDCl3 proton);

 

str4

TOFMS: [C17H21NO4 + H+]: calculated 304.1543, found 304.1703(100%).

str5

 

UPLC conditions were as follows for compound 11; Acquity Waters, column: BEH C18 (2.1 mm X 100 mm) 1.7 µm with mobile phases A (0.05% TFA in water) and B (acetonitrile). Detection was at 220 nm, flow was set at 0.4 mL/min, and the temperature was 30 °C (Run time: 9 min). Gradient: 0 min, A = 90%, B = 10%; 0.5 min, A = 90%, B = 10%; 6.0 min, A = 0%, B = 100%; 7.5 min, A = 0%, B = 100%; 7.6 min, A = 90%, B = 10%; 9.0 min, A = 90%, B = 10%.

 

Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate) (11)

as a yellow oil. % purity: 93.4% (UPLC);
1H NMR (CDCl3, 400 MHz) δ: 3.23 (dd, J1 = 1.6 Hz, J2 = 6.0 Hz, 4H), 3.62 (s, 2H), 3.75 (s, 6H), 6.07 (dt, J1 = 1.6 Hz, J2 = 16.0 Hz, 2H), 6.97 (dt, J1 = 6.0 Hz, J2 = 16.0 Hz, 2H), 7.25–7.34 (m, 5H-merged with CDCl3 proton);
13C NMR (CDCl3, 100 MHz) δ: 51.53, 53.42, 58.37, 122.66, 127.28, 128.41, 128.55, 128.76, 138.24, 145.84, 166.58;
IR (CHCl3): ν = 758, 1215, 1278, 1437, 1660, 1720, 2806, 2953, 3020, 3421 cm–1;
TOFMS: [C17H21NO4 + H+]: calculated 304.1543, found 304.1703(100%).
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00399
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1-Bromo-4-fluoro-2-((2-iodobenzyl)oxy)benzene

 Uncategorized  Comments Off on 1-Bromo-4-fluoro-2-((2-iodobenzyl)oxy)benzene
Jan 252017
 

STR1

1-Bromo-4-fluoro-2-((2-iodobenzyl)oxy)benzene

CAS 1161931-51-6

STR1 STR2

Mp 89.8–92.3 °C.

IR (neat, ATR): 3072 (w), 1482 (s), 1451 (s), 1294 (s), 1294 (s) cm–1.

1H NMR (399 MHz, DMSO-d6) δ 5.12 (s, 2H), 6.81 (td, J = 8.49, 2.77 Hz, 1H), 7.14 (td, J = 7.64, 1.65 Hz, 1H), 7.18 (dd, J = 10.90, 2.82 Hz, 1H), 7.46 (td, J = 7.52, 0.92 Hz, 1H), 7.60 (dd, J = 7.64, 1.41 Hz, 1H), 7.62 (dd, J = 8.66, 6.23 Hz, 1H), 7.92 (dd, J = 7.83, 0.83 Hz, 1H).

13C NMR (100 MHz, DMSO-d6) δ 74.5, 99.2, 102.4 (d, J = 27.1 Hz), 105.8 (d, J = 3.4 Hz), 108.9 (d, J = 22.5 Hz), 128.5, 129.8, 130.3, 133.6 (d, J = 9.9 Hz), 138.0, 139.2, 155.4 (d, J = 10.7 Hz), 162.2 (d, J = 244.3 Hz).

GCMS: m/z [M]+ calcd for C13H9BrFIO: 405.88600; found: 405.88620.

1H AND 13C NMR PREDICT

STR1 STR2 STR3 str4

 

Org. Process Res. Dev., Article ASAP

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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Brc2ccc(F)cc2OCc1ccccc1I
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