AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER
Feb 092017
 

STR1

 

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

STR1 STR2

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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Feb 092017
 

STR1 STR2 STR3

(±)-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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Feb 012017
 

 

STR1

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

STR1 STR2 STR3 str4 str5

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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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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One-Pot Reductive Cyclisations of Nitroanilines to Imidazoles

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on One-Pot Reductive Cyclisations of Nitroanilines to Imidazoles
Jan 252017
 

Hana and co-workers ( Synlett 2010, 18, 2759−2764) from Genentech have developed a single-step procedure for conversion of 2-nitro aromatic amines to benzimidazoles. Addition of ammonium chloride proved necessary as Fe powder and formic acid alone was ineffective for nitro reduction. These conditions were compatible with a variety of functional groups on the aromatic, including boronate esters. The methodology was also extended to nitro aminopyridines but failed to deliver the desired product with isoxazole or pyrazole reactants.

Mild and General One-Pot Reduction and Cyclization of Aromatic and Heteroaromatic 2-Nitroamines to Bicyclic 2H-Imidazoles

Emily J. Hanan*, Bryan K. Chan, Anthony A. Estrada, Daniel G. Shore, Joseph P. Lyssikatos

*Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA, Email: hanan.emilygene.com

E. J. Hanan, B. K. Chan, A. A. Estrada, D. G. Shore, J. P. Lyssikatos, Synlett, 2010, 2759-2764.

DOI: 10.1055/s-0030-1259007


see article for more reactions

Abstract

A one-pot procedure for the conversion of aromatic and heteroaromatic 2-nitroamines into bicyclic 2H-benzimidazoles employs formic acid, iron powder, and NH4Cl as additive to reduce the nitro group and effect the imidazole cyclization with high-yielding conversions generally within one to two hours. The compatibility with a wide range of functional groups demonstrates the general utility of this procedure.


see article for more examples

//////////One-Pot, Reductive Cyclisations,  Nitroanilines,  Imidazoles

“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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A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

 PROCESS, spectroscopy, SYNTHESIS  Comments Off on A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines
Jan 062017
 

Graphical abstract: A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

 

We have reported herein a catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles by which a series of five-ring-fused tetrahydroisoquinolines featuring an indoline scaffold were obtained as single diastereomers in moderate to high yields without any additives under mild conditions. Moreover, the current method provides a novel and convenient approach for the efficient incorporation of two biologically important scaffolds (tetrahydroisoquinoline and indoline).

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C6GC02517J?utm_medium=email&utm_campaign=pub-GC-vol-19-issue-1&utm_source=toc-alert#!divAbstract

A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

Xihong Liu,a   Dongxu Yang,a   Kezhou Wang,a  Jinlong Zhanga and   Rui Wang*ab  
*Corresponding authors
aSchool of Life Sciences, Institute of Biochemistry and Molecular Biology, Lanzhou University, Lanzhou 730000, P. R. China
E-mail: wangrui@lzu.edu.cn
bState Key Laboratory of Chiroscience, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, P. R. China
E-mail: bcrwang@polyu.edu.hk
Green Chem., 2017,19, 82-87

DOI: 10.1039/C6GC02517J

 

 ethyl 13b-nitro-8-tosyl-8,8a,13b,13c-tetrahydro-5H-indolo[2′,3′:3,4]pyrazolo[5,1- a]isoquinoline-9(6H)-carboxylate: White solid, m.p. 153 – 154 oC; 94% yield;
1H NMR (300 MHz, CDCl3) δ 7.86 (d, J = 8.2 Hz, 2H), 7.78 (d, J = 7.9 Hz, 1H), 7.30 – 7.13 (m, 5H), 7.1 (s, 1H), 7.05 – 6.94 (m, 1H), 6.94 – 6.87 (m, 1H), 6.59 (t, J = 7.6 Hz, 3H), 6.28 (d, J = 7.6 Hz, 1H), 4.78 (s, 1H), 4.37 (q, J = 7.1 Hz, 2H), 2.80 – 2.58 (m, 2H), 2.33 (s, 3H), 2.31 – 2.11 (m, 2H), 1.41 (t, J = 7.1 Hz, 3H) ppm;
13C NMR (75 MHz, CDCl3) δ 152.1, 144.6, 142.6, 134.0, 132.1, 129.3, 129.0, 128.7, 128.3, 127.5, 127.3, 126.2, 122.8, 121.1, 115.5, 104.5, 84.9, 70.7, 62.8, 48.5, 29.1, 21. 6, 14.3 ppm;
HRMS (ESI): C27H26N4NaO6S [M + Na]+ calcd: 557.1465, found: 557.1476.

“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

/////////// catalyst-free,  1,3-dipolar cycloaddition, C,N-cyclic azomethine imines,  3-nitroindoles,  five-ring-fused tetrahydroisoquinolines
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One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases

 spectroscopy, SYNTHESIS  Comments Off on One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases
Dec 252016
 

Graphical abstract: One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases

One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases

Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC03023H, Communication
P. Matzel, M. Gand, M. Hohne
Imine reductases (IREDs) show great potential as catalysts for reductive amination of ketones to produce chiral secondary amines.

One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases

Imine reductases (IREDs) show great potential as catalysts for reductive amination of ketones to produce chiral secondary amines. In this work, we explored this potential and synthesized the pharmaceutically relevant (R)-rasagiline in high yields (up to 81%) and good enantiomeric excess (up to 90% ee) from the ketone precursor. This one-step approach in aqueous medium represents the shortest synthesis route from achiral starting materials. Furthermore, we demonstrate for the first time that tertiary amines also can be accessed by this route, which provides new opportunities for eco-friendly enzymatic asymmetric syntheses of these important molecules.

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C6GC03023H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

One-step asymmetric synthesis of (R)- and (S)-rasagiline by reductive amination applying imine reductases

P. Matzel,a   M. Gandb and   M. Höhne*a  
*Corresponding authors
aInstitute of Biochemistry, Greifswald University, Felix-Hausdorff-Str. 4, 17487 Greifswald, Germany
E-mail: Matthias.Hoehne@uni-greifswald.de
bBiocenter Klein Flottbek, University of Hamburg, Ohnhorststr. 18, 22609 Hamburg, Germany
Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC03023H

str0 str1 str2 str3 str4

////////////One-step, asymmetric synthesis,  (R)- ,  (S)-rasagiline,  reductive amination,  imine reductases

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Synthesis of (E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene)aniline

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Synthesis of (E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene)aniline
Dec 212016
 

str1

Cas 1204588-48-6
MF C21 H20 N4 O4
MW 392.41
Benzenamine, 2,​4-​dinitro-​N-​[(2E,​4E)​-​4-​phenyl-​5-​(1-​pyrrolidinyl)​-​2,​4-​pentadien-​1-​ylidene]​-​, [N(E)​]​-
(E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene)aniline
str1

 

 

Molbank 2009, 2009(3), M604; doi:10.3390/M604

Synthesis of (E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene)aniline
Nosratollah Mahmoodi 1,*, Manuchehr Mamaghani 1, Ali Ghanadzadeh 2, Majid Arvand 3 and Mostafa Fesanghari 1
1Laboratory of Organic Chemistry, Faculty of Science, University of Guilan, P.O.Box 1914, Rasht, Iran,
2Departments of Physical Chemistry, Faculty of Science, University of Guilan, P.O.Box 1914, Rasht, Iran
3Departments of Analytical Chemistry, Faculty of Science, University of Guilan, P.O.Box 1914, Rasht, Iran
*Author to whom correspondence should be addressed
mahmoodi@guilan.ac.ir, m-chem41@guilan.ac.ir, aggilani@guilan.ac.ir, arvand@guilan.ac.ir, nosmahmoodi@gmail.com

Abstract:

(E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene) aniline dye was prepared in one pot by reaction of premade N-2,4-dinitrophenyl-3-phenylpyridinium chloride (DNPPC) and pyrrolidine in absolute MeOH.
Keywords:

N-2,4-dinitrophenyl-3-phenylpyridinium chloride (DNPPC); photochromic; pyridinium salt

N-2,4-Dinitrophenyl-3-phenylpyridinium chloride (DNPPC) 1 was prepared according to the literature method [1,2,3,4,5,6,7]. Recently, we became interested in the synthesis of photochromic compounds [8,9,10]. The UV-Vis spectra under irradiation of UV light of dye 2 indicate photochromic properties for this molecule. The salt 1 was premade and typically isolated and purified by recrystallization and characterized. To a solution of 1-chloro-2,4-dinitrobenzene (1.42 g, 7.01 mmol) in acetone (10 mL) was added 3-phenylpyridine (1.0 mL, 6.97 mmol). The reaction was heated at reflux for 48 h. The solvent was removed under reduced pressure and the red residue was stirred in hexanes. The precipitated product was collected by vacuum filtration to afford pure pyridinium salt 1 as a reddish brown solid (2.23 g, 6.25 mmol, 90%). 1H NMR (CDCl3, 500 MHz): δ (ppm) 9.9 (s, 1H), 9.4 (d, J = 6.0 Hz, 1H), 9.3 (d, J = 8.3 Hz, 1H), 9.2 (d, J = 2.2 Hz, 1H), 9.0 (dd, J = 8.7, 2.4 Hz, 1H), 8.5-8.6 (m, 2H), 8.0 (d, J = 7.3 Hz, 2H), 7.6- 7.7 (m, 3H); 13C NMR (CDCl3, 125 MHz): δ (ppm) 149.2, 145.6, 144.3, 144.2, 143.0, 139.2, 138.7, 132.5, 132.3, 130.6, 130.2, 129.6, 128.0, 127.6, 121.3; IR (KBr pellet) 3202, 3129, 2994, 2901, 1609 cm-1; m. p. = 182-183 °C; HRMS m/z Calcd for C17H12N3O4+ (M)+ 322.0828, found 322.0836.
Molbank 2009 m604 i001
Reaction of pyrrolidine with salt (1) leads to the opening of the pyridinium ring and formation of dye 2. This dye was prepared from reaction of salt 1 (0.5 g, 1.4 mmol) in 5 mL absolute MeOH after cooling a reaction mixture to -10oC and keeping at this temperature for 15 min. To this was added pyrrolidine (0.1 g, 1.4 mmol) in 3 mL absolute MeOH over a period of 10 min. The prepared solid was filtered, washed with CH2Cl2, dried and recrystallized from n-hexane to yield 68% (0.37 g, 0.95 mmol) of pure metallic greenish-brown 2,
m.p. = 146 oC.
IR (KBr): 3040, 2950, 1616, 1514, 1492, 1469, 1321, 1215, 1170, 1105, 956, 904, 862, 727 cm-1.
1H NMR (500 MHz, CDCl3): δ (ppm) 8.7 (d, J = 2.4 Hz, 1H) 8.3 (dd, J = 2.4, 8.84 Hz, 1H), 8.0 (s, 1H), 7.5 (d, J = 7.4 Hz, 2H), 7.4-7.5 (t, J = 7.5 Hz, 2H), 7.3-7.4 (m, 1H), 7.2 (d, J = 12.5 Hz, 1H), 7.1 (d, J = 8.9 Hz, 1H), 7.0 (d, J = 12.1 Hz, 1H), 5.4 (t, J = 12.2 Hz, 1H), 3.3 (br, 4H), 2.0 (br, 4H);
13C NMR (125 MHz, CDCl3): δ (ppm) 22.0, 55.6, 114.7, 117.4, 120.0, 124.1, 126.4, 128.7, 128,8, 129.0, 132.7, 137.1, 137.3, 142.9, 147.8, 150.2, 163.8.
Anal. Calcd for C21H20N4O4: %C = 64.28, %H = 5.14, %N = 14.28. Found: %C = 64.08, %H = 5.11, %N = 14.07.

str1

 

 

1H NMR PREDICT

str0

ACTUAL….

1H NMR (500 MHz, CDCl3): δ (ppm) 8.7 (d, J = 2.4 Hz, 1H) 8.3 (dd, J = 2.4, 8.84 Hz, 1H), 8.0 (s, 1H), 7.5 (d, J = 7.4 Hz, 2H), 7.4-7.5 (t, J = 7.5 Hz, 2H), 7.3-7.4 (m, 1H), 7.2 (d, J = 12.5 Hz, 1H), 7.1 (d, J = 8.9 Hz, 1H), 7.0 (d, J = 12.1 Hz, 1H), 5.4 (t, J = 12.2 Hz, 1H), 3.3 (br, 4H), 2.0 (br, 4H);

str0

 

13 C NMR PREDICT

 

str1

ACTUAL…….13C NMR (125 MHz, CDCl3): δ (ppm) 22.0, 55.6, 114.7, 117.4, 120.0, 124.1, 126.4, 128.7, 128,8, 129.0, 132.7, 137.1, 137.3, 142.9, 147.8, 150.2, 163.8.

str3

////////////Synthesis, (E)-2,4-Dinitro-N-((2E,4E)-4-phenyl-5-(pyrrolidin-1-yl)penta-2,4-dienylidene)aniline

[O-][N+](=O)c3ccc(\N=C\C=C\C(=C/N1CCCC1)c2ccccc2)c([N+]([O-])=O)c3

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Synthesis of 2-[4-(4-Chlorophenyl)piperazin-1-yl]-2-methylpropanoic Acid Ethyl Ester

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Synthesis of 2-[4-(4-Chlorophenyl)piperazin-1-yl]-2-methylpropanoic Acid Ethyl Ester
Dec 202016
 
str1
2-[4-(4-Chlorophenyl)piperazin-1-yl]-2-methylpropanoic Acid Ethyl Ester
1-Piperazineacetic acid, 4-(4-chlorophenyl)-α,α-dimethyl-, ethyl ester
2-[4-(4-Chlorophényl)-1-pipérazinyl]-2-méthylpropanoate d‘éthyle
Ethyl 2-[4-(4-chlorophenyl)-1-piperazinyl]-2-methylpropanoate
Ethyl-2-[4-(4-chlorphenyl)-1-piperazinyl]-2-methylpropanoat
1206769-44-9
2-[4-(4-Chlorophenyl)piperazin-1-yl]-2-methylpropanoic Acid Ethyl Ester (en)
AGN-PC-0JIRMK
AKOS016034964
ethyl 2-[4-(4-chlorophenyl)piperazin-1-yl]-2-methylpropanoate
MWt310.819
MFC16H23ClN2O2
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1H NMR PREDICT
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ACTUAL VALUES……..1H NMR (400 MHz, CDCl3): δ ppm 1.27 (t, 3H, J = 7.2 Hz, -CH2-CH3), 1.35 (s, 6H, 2 x CH3), 2.74-2.76 (m, 4H, J = 4.8 Hz, -CH2-N-CH2-), 3.14-3.17 (m, 4H, J = 4.8 Hz, -CH2-N-CH2-), 4.20 (q, 2H, J = 7.2 Hz, -CH2-CH3), 6.81-6.83 (d, 2H, J = 6.8 Hz, phenyl protons), 7.17-7.20 (d, 2H, J = 6.8 Hz, phenyl protons).
str1
13C NMR PREDICT
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ACTUAL VALUES……..13C NMR (100 MHz, CDCl3): δ ppm 14.3 (CH3), 22.7 ((CH3)2), 46.6 (-CH2-N-CH2-), 49.7 (-CH2-N-CH2-), 60.5 (O-CH2), 62.4 (N-C-), 117.0, 124.3, 128.8, 149.8 (aromatic carbons), 174.3 (C=O).
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Paper

To a solution of 4-(4-chlorophenyl)piperazine dihydrochloride 1 (5.0 g, 0.0185 mol) in DMSO (30 ml), anhydrous cesium carbonate (30.0 g, 0.0925 mol), sodium iodide (1.39 g, 0.0093 mol) and ethyl 2-bromo-2-methylpropanoate 2 (3.97 g, 0.02 mol) were added. The resulting mixture was stirred at 25-30oC for 12 hours. The reaction mass was diluted with water (200 ml) and extracted with ethyl acetate (2 x 200 ml). The ethyl acetate layer was washed with water (2 x 100 ml), dried over anhydrous sodium sulfate (10.0 g) and concentrated under vacuum. The crude product thus obtained was purified by column chromatography (stationary phase silica gel 60-120 mesh; mobile phase 10% ethyl acetate in hexane). The title compound 3 was obtained as a white solid (4.73 g, 82 %).

Molbank 2009 m607 i001
Melting Point: 56oC.
EI-MS m/z (rel. int. %): 311 (100) [M+1]+, 236(40), 197(60), 154(45).
IR ν max (KBr) cm-1: 2839-2996 (C-H aliphatic); 1728 (C=O), 1595, 1505 (C=C aromatic), 1205 (C-O bending), 758 (C-Cl bending).
1H NMR (400 MHz, CDCl3): δ ppm 1.27 (t, 3H, J = 7.2 Hz, -CH2-CH3), 1.35 (s, 6H, 2 x CH3), 2.74-2.76 (m, 4H, J = 4.8 Hz, -CH2-N-CH2-), 3.14-3.17 (m, 4H, J = 4.8 Hz, -CH2-N-CH2-), 4.20 (q, 2H, J = 7.2 Hz, -CH2-CH3), 6.81-6.83 (d, 2H, J = 6.8 Hz, phenyl protons), 7.17-7.20 (d, 2H, J = 6.8 Hz, phenyl protons).
13C NMR (100 MHz, CDCl3): δ ppm 14.3 (CH3), 22.7 ((CH3)2), 46.6 (-CH2-N-CH2-), 49.7 (-CH2-N-CH2-), 60.5 (O-CH2), 62.4 (N-C-), 117.0, 124.3, 128.8, 149.8 (aromatic carbons), 174.3 (C=O).
Elemental analysis: Calculated for C16H23ClN2O2: C, 61.83%, H, 7.46%, N, 9.01%; Found: C, 61.90%, H, 7.44%, N, 8.98%.
Molbank 2009, 2009(3), M607; doi:10.3390/M607

Synthesis of 2-[4-(4-Chlorophenyl)piperazin-1-yl]-2-methylpropanoic Acid Ethyl Ester

1Department of Chemistry, Sambalpur University, JyotiVihar-768019, Orissa, India
2Institute of Chemical Technology (ICT), Matunga, Mumbai-400019, Maharashtra, India
*Author to whom correspondence should be addressed.
Received: 17 May 2009 / Accepted: 30 June 2009 / Published: 27 July 2009
Bijay K Mishra

Professor at Sambalpur University, Chemistry Department

Abstract

The title compound was synthesized by N-alkylation of 4-(4-chlorophenyl)piperazine with ethyl 2-bromo-2-methylpropanoate and its IR, 1H NMR, 13C NMR and Mass spectroscopic data are reported.

 

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CCOC(=O)C(N1CCN(CC1)c1ccc(cc1)Cl)(C)C

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An Efficient Synthesis of 1-(2-Methoxyphenoxy)-2,3-epoxypropane: Key Intermediate of β-Adrenoblockers

 spectroscopy, SYNTHESIS  Comments Off on An Efficient Synthesis of 1-(2-Methoxyphenoxy)-2,3-epoxypropane: Key Intermediate of β-Adrenoblockers
Nov 302016
 

Abstract Image

An efficient process for the preparation of 1-(2-methoxyphenoxy)-2,3-epoxypropane, a key intermediate for the synthesis of ranolazine is described.

http://pubs.acs.org/doi/suppl/10.1021/op300056k

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Preparation of 1-(2-Methoxyphenoxy)-2,3-epoxypropane 4.

To a stirring solution of 2-methoxy phenol 2 (10 kg, 80.55 mol) and water (40 L) at about 30 °C was added sodium hydroxide (1.61 kg, 40.25 mol) and water (10 L). After stirring for 30−45 min, epichlorohydrin 3 (22.35 kg, 241.62 mol) was added and stirred for 10−12 h at 25−35 °C. Layers were separated, and water (40 L) was added to the organic layer (bottom layer) containing product. Sodium hydroxide solution (3.22 kg, 80.5 mol) and water (10 L) were added at 27 °C and stirred for 5−6 h at 27 °C.

The bottom product layer was separated and washed with sodium hydroxide solution (3.0 kg 75 mol) and water (30 L). Excess epichlorohydrin (3) was recovered by distillation of the product layer at below 90 °C under vacuum (650−700 mmHg) to give 13.65 kg (94%) of title compound with 98.3% purity by HPLC, 0.2% of 2- methoxy phenol 2, 0.1% of epichlorohydrin 3, 0.1% of chlorohydrin 11, 0.3% of dimer 12 and 0.3% of dihydroxy 13.

1 H NMR (400 MHz, CDCl3, δ) 6.8−7.0 (m, 4H), 4.3 (dd, J = 5.6 Hz, 5.4 Hz, 1H), 3.8 (dd, J = 5.6 Hz, 5.3 Hz, 1H), 3.7 (s, 3H), 3.2−3.4 (m, 1H), 2.8 (dd, J = 5.6 Hz, 5.4 Hz, 1H), 2.7 (dd, J = 5.6 Hz, 5.3 Hz, 1H);


IR (KBr, cm−1 ) 2935 (C−H, aliphatic), 1594 and 1509 (CC, aromatic), 1258 and 1231 (C−O−C, aralkyl ether), 1125 and 1025 (C−O−C, epoxide);


MS (m/z) 181 (M+ + H).



Compound Details

Properties
MWt 180.2
MF C10H12O3


CAS 2210-74-4

Glycidyl 2-methoxyphenyl ether
Guaiacol glycidyl ether

1H NMR PREDICT

13C NMR PREDICT

COSY PREDICT

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CREDIT……….http://www.molbase.com/en/synthesis_2210-74-4-moldata-95563.html

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RakeshwarBandichhor

DR REDDYS LABORATORIES

An Efficient Synthesis of 1-(2-Methoxyphenoxy)-2,3-epoxypropane: Key Intermediate of β-Adrenoblockers

 Innovation Plaza, IPD, R&D, Dr. Reddy’s Laboratories Ltd., Survey Nos. 42, 45,46, and 54, Bachupally, Qutubullapur – 500073, Andhra Pradesh, India

 Institute of Science and Technology, Center for Environmental Science, JNT University, Kukatpally, Hyderabad – 500 072, Andhra Pradesh, India

Org. Process Res. Dev.201216 (10), pp 1660–1664

DOI: 10.1021/op300056k

Publication Date (Web): September 14, 2012

Copyright © 2012 American Chemical Society

*Telephone: +91 4044346000. Fax: +91 4044346285. E-mail: rakeshwarb@drreddys.com.

////////////////1-(2-Methoxyphenoxy)-2,3-epoxypropane,  β-Adrenoblockers, ranolazine


COc2ccccc2OCC1CO1



OTHER COMPD

Glycidyl 2-methylphenyl ether technical grade, 90%


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