A Practical Asymmetric Synthesis of Isopropyl (1R,2S)-Dehydrocoronamate

被引：18

作者：

Tang, Wenjun ^{[1
]}

Wei, Xudong ^{[1
]}

Yee, Nathan K. ^{[1
]}

Patel, Nitinchandra ^{[1
]}

Lee, Heewon ^{[1
]}

Savoie, Jolaine ^{[1
]}

Senanayake, Chris H. ^{[1
]}

机构：

[1] Boehringer Ingelheim Pharmaceut Inc, Chem Dev, Ridgefield, CT 06877 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2011年 / 15卷 / 05期

关键词：

HEPATITIS-C VIRUS; NS3; PROTEASE; INHIBITORS; ACIDS; CYCLOPROPANES; REARRANGEMENT; BILN-2061;

D O I：

10.1021/op200038y

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A novel asymmetric synthesis of isopropyl (1R,2S)-dehydrocoronamate is described from (S)-1,2,4-butanetriol as the starting material in 28% overall yield. Highlights of this synthetic route include selective cyclopropanation between chiral cyclic sulfate 5 and diisopropyl malonate (8c), formation of vinylcyclopropane 3c via elimination of halide 4c, selective monohydrolysis of diisopropyl ester 3c, and Curtius rearrangement of acid 10 to form isopropyl (1R,2S)-dehydrocoronamate TsOH salt 13 in >99% ee. With the involvement of only three isolations, this chromatography-free process provides a rapid and practical access to (1R,2S)-1-amino-2-vinylcyclopropane-1-carboxylic acid derivatives.

引用

页码：1207 / 1211

页数：5

共 25 条

[1] Synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) derivatives:: Key intermediates for the preparation of inhibitors of the hepatitis C virus NS3 protease [J].

Beaulieu, PL ;

Gillard, J ;

Bailey, MD ;

Boucher, C ;

Duceppe, JS ;

Simoneau, B ;

Wang, XJ ;

Zhang, L ;

Grozinger, K ;

Houpis, I ;

Farina, V ;

Heimroth, H ;

Krueger, T ;

Schnaubelt, J .

JOURNAL OF ORGANIC CHEMISTRY, 2005, 70 (15) :5869-5879

[2] Enantioselective Synthesis of (1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic Acid Ethyl Ester (Vinyl-ACCA-0Et) by Asymmetric Phase-Transfer Catalyzed Cyclopropanation of (E)-N-Phenylmethyleneglycine Ethyl Ester [J].

Belyk, Kevin M. ;

Xiang, Bangping ;

Bulger, Paul G. ;

Leonard, William R., Jr. ;

Balsells, Jaume ;

Yin, Jingjun ;

Chen, Cheng-yi .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2010, 14 (03) :692-700

[3] Large-scale oxidations in the pharmaceutical industry [J].

Caron, Stephane ;

Dugger, Robert W. ;

Ruggeri, Sally Gut ;

Ragan, John A. ;

Ripin, David H. Brown .

CHEMICAL REVIEWS, 2006, 106 (07) :2943-2989

[4] Total synthesis of (+)-phyllantidine [J].

Carson, Cheryl A. ;

Kerr, Michael A. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2006, 45 (39) :6560-6563

[5] Synthesis of Methyl-1-(tert-butoxycarbonylamino)-2-vinylcyclopropanecarboxylate via a Hofmann Rearrangement Utilizing Trichloroisocyanuric Acid as an Oxidant [J].

Crane, Zackary D. ;

Nichols, Paul J. ;

Sammakia, Tarek ;

Stengel, Peter J. .

JOURNAL OF ORGANIC CHEMISTRY, 2011, 76 (01) :277-280

[6]

Donkor IO, 2000, CHIRALITY, V12, P551, DOI 10.1002/1520-636X(2000)12:7<551::AID-CHIR1>3.3.CO

[7]

2-3

[8]

Dorizon P, 1998, SYNLETT, P483

[9] Stereoselective synthesis of highly functionalized cyclopropanes.: Application to the asymmetric synthesis of (1S,2S)-2,3-methanoamino acids [J].

Dorizon, P ;

Su, GF ;

Ludvig, G ;

Nikitina, L ;

Paugam, R ;

Ollivier, J ;

Salaün, J .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (13) :4712-4724

[10]

Ende DJA, 1998, ORG PROCESS RES DEV, V2, P382

← 1 2 3 →