The Large-Scale Synthesis of (S)-N-Boc-bis(4-fluorophenyl)alanine

被引：23

作者：

Appell, Robert B. ^{[1
]}

Boulton, Lee T. ^{[2
]}

Daugs, Edward D. ^{[1
]}

Hansen, Matt ^{[1
]}

Hanson, Christopher H. ^{[3
]}

Heinrich, Jerry ^{[1
]}

Kronig, Christel ^{[2
]}

Lloyd, Richard C. ^{[2
]}

Louks, David ^{[1
]}

Nitz, Mark ^{[1
]}

Praquin, Celine ^{[2
]}

Ramsden, James A. ^{[2
]}

Samuel, Helen ^{[2
]}

Smit, Mark ^{[1
]}

Willets, Matthew ^{[3
]}

机构：

[1] Dow Chem Co USA, Midland, MI 48674 USA

[2] Dr Reddys Labs Ltd, Chirotech Technol Ctr, Cambridge CB4 0PE, England

[3] Dr Reddys Labs EU Ltd, Mirfield WF14 8HZ, W Yorkshire, England

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2013年 / 17卷 / 01期

关键词：

ASYMMETRIC CATALYSIS; HYDROGENATION; LIGAND;

D O I：

10.1021/op3002855

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

The synthesis of (S)-N-Boc-bis(4-fluorophenyl)alanine, an intermediate in the synthesis of denagliptin, is described from the synthesis of a 12 g proof of principle sample to a >900 kg cGMP manufacturing campaign. The chiral centre was established by the asymmetric hydrogenation of the sterically crowded precursor, ethyl 2-acetamido-3,3-bis(4-fluorophenyl)acrylate. The ability to isolate the various intermediates in a physical form that would readily allow filtration, washing, and ultimately purification underpinned the successful manufacturing campaign.

引用

页码：69 / 76

页数：8

共 14 条

[1]

[Anonymous], MODDE DES EXP 6 0

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