Chemical development of CI-1008, an enantiomerically pure anticonvulsant

被引：133

作者：

Hoekstra, MS ^{[1
]}

Sobieray, DM ^{[1
]}

Schwindt, MA ^{[1
]}

Mulhern, TA ^{[1
]}

Grote, TM ^{[1
]}

Huckabee, BK ^{[1
]}

Hendrickson, VS ^{[1
]}

Franklin, LC ^{[1
]}

Granger, EJ ^{[1
]}

Karrick, GL ^{[1
]}

机构：

[1] Warner Lambert Parke Davis, Holland, MI 49423 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 1997年 / 1卷 / 01期

关键词：

D O I：

10.1021/op9600320

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Development of a manufacturing process for (S)-3-(aminomethyl)-5-methylhexanoic acid, an anticonvulsant, is described. Initial preparation employed an Evans chiral alkylation on (4R,5S)-4-methyl-3-(1-oxo-4-methylpentyl)-5-phenyl-2-oxazolidinone, using benzyl bromoacetate. Use of tert-butyl bromoacetate proved advantageous for large-scale preparation. Route selection for a low-cost manufacturing process was based on "ideal process" cost projections. Four routes were evaluated in the laboratory. Of the four, two were scaled up in the pilot plant, resulting in selection of a route based on synthesis of racemic 3-(aminomethyl)-5-methylhexanoic acid, followed by resolution with (S)-(+)-mandelic acid.

引用

页码：26 / 38

页数：13

共 17 条

[1]

ANDRUSKIEWICZ R, 1990, SYNTHETIC COMMUN, P159

[2]

BERGERON RJ, 1984, SYNTHESIS-STUTTGART, P782

[3] DIHYDROISOCOUMARINS .10. PREPARATION + REDUCTION OF SOME O-CARBOXYPHENYLACETATES [J].