An enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid via asymmetric hydrogenation

被引：97

作者：

Burk, MJ

de Koning, PD

Grote, TM

Hoekstra, MS

Hoge, G

Jennings, RA

Kissel, WS

Le, TV

Lennon, IC

Mulhern, TA

Ramsden, JA

Wade, RA

机构：

[1] Chirotech Technol Ltd, Dowpharma, Cambridge CB4 0WG, England

[2] Pfizer Inc, Pfizer Global Res & Dev, Holland, MI 49424 USA

[3] Pfizer Inc, Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2003年 / 68卷 / 14期

关键词：

D O I：

10.1021/jo034397b

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A concise enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid (1, Pregabalin) has been developed. The key step is the asymmetric hydrogenation of a 3-cyano-5-methylhex-3-enoic acid salt 2 with a rhodium Me-DuPHOS catalyst, providing the desired (S)3-cyano-5-methylhexanoate 3 in very high ee. Subsequent hydrogenation of the nitrile 3 with a heterogeneous nickel catalyst provides Pregabalin 1 in excellent overall yield and purity.

引用

页码：5731 / 5734

页数：4

共 16 条

[1] A SIMPLE SYNTHESIS OF 2-(1-HYDROXYALKYL)ACRYLONITRILES [J].

BASAVAIAH, D ;

GOWRISWARI, VVL .

SYNTHETIC COMMUNICATIONS, 1987, 17 (05) :587-591

[2]

Berens U, 2000, ANGEW CHEM INT EDIT, V39, P1981, DOI 10.1002/1521-3773(20000602)39:11<1981::AID-ANIE1981>3.0.CO

[3]

2-3

[4]

Burk MJ, 1998, ANGEW CHEM INT EDIT, V37, P1931, DOI 10.1002/(SICI)1521-3773(19980803)37:13/14<1931::AID-ANIE1931>3.0.CO

[5]

2-3

[6] Me-DuPHOS-Rh-catalyzed asymmetric synthesis of the pivotal glutarate intermediate for candoxatril [J].

Burk, MJ ;

Bienewald, F ;

Challenger, S ;

Derrick, A ;

Ramsden, JA .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (09) :3290-3298

[7]

BURK MJ, 2001, Patent No. 0155090

[8] Chemical development of CI-1008, an enantiomerically pure anticonvulsant [J].

Hoekstra, MS ;

Sobieray, DM ;

Schwindt, MA ;

Mulhern, TA ;

Grote, TM ;

Huckabee, BK ;

Hendrickson, VS ;

Franklin, LC ;

Granger, EJ ;

Karrick, GL .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 1997, 1 (01) :26-38

[9]

JENDRALLA H, 1993, SYNLETT, P155

[10] ASYMMETRIC HYDROGENATION OF PROCHIRAL ALKENES CATALYZED BY RUTHENIUM COMPLEXES OF (R)-(+)-2,2'-BIS(DIPHENYLPHOSPHINO)-1,1'-BINAPHTHYL [J].

KAWANO, H ;

IKARIYA, T ;

ISHII, Y ;

SABURI, M ;

YOSHIKAWA, S ;

UCHIDA, Y ;

KUMOBAYASHI, H .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1989, (09) :1571-1575

← 1 2 →