Large-Scale Synthesis of Chiral Tetrahydropyran via Asymmetric Allylation Catalyzed by (S)-3,3?-Cl2-BINOL

被引：2
|
作者：
Li, Ning [1 ]
Li, Guisheng [1 ]
Konrad, Michael [2 ]
Kressierer, Christoph [2 ]
Betzemeier, Bodo [2 ]
Kosnik, Stephanie C. [1 ,3 ]
Wu, Lifen [1 ,3 ]
Pennino, Scott [1 ,3 ]
Lee, Heewon [1 ]
Zhang, Yongda [1 ]
机构：
[1] Boehringer Ingelheim Pharmaceut Inc, Chem Dev, Ridgefield, CT 06877 USA
[2] Boehringer Ingelheim Pharm GmbH & Co KG, Chem Dev, D-88397 Biberach, Germany
[3] Boehringer Ingelheim Pharmaceut Inc, Mat & Analyt Sci, Ridgefield, CT 06877 USA
来源：
ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2022年 / 26卷 / 10期
关键词：
PDE2; tetrahydropyran; allylation; 3; 3?-Cl2-BINOL; organocatalyst; ENANTIOSELECTIVE SYNTHESIS; EPOXIDE OPENINGS; RECENT PROGRESS; KETONES; INHIBITOR; 6-ENDO; PHOSPHODIESTERASE; METHALLYLATION; ALLYLBORATION; ACTIVATION;
D O I：
10.1021/acs.oprd.2c00258
中图分类号：
O69 [应用化学];
学科分类号：
081704 ;
摘要：
Asymmetric synthesis of chiral tetrahydropyran 3, a key intermediate of PDE2 inhibitor 1, has been achieved in five linear steps with a 49% overall yield and >99:1 er on a large scale. The whole chemical process was realized without silica gel chromatography purification, starting from tert-butyl 2-chloro-5-(2-chloroacetyl)benzoate 7. The key features of current synthesis include asymmetric allylation catalyzed by an organocatalyst (S)-3,3 '-Cl2-BINOL under solvent-free conditions.
引用
收藏
页码：2973 / 2978
页数：6
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