A concise, stereoselective and scalable synthesis of optically pure (3R,4R)-1-benzyl- and (3R,4R)-1-Boc-3-methyl-4-aminopiperidines

被引：0

作者：

Hazra, Sunit ^{[1
]}

Kangune, Ankit ^{[1
]}

Pawar, Govind ^{[1
]}

Karmakar, Ananta ^{[1
]}

Pabbisetty, Kumar B. ^{[3
]}

Mortensen, Deborah S. ^{[4
]}

Dodd, Dharmpal S. ^{[4
]}

Li, Jianqing ^{[2
]}

Mathur, Arvind ^{[3
]}

Gupta, Anuradha ^{[1
]}

Nimje, Roshan Y. ^{[1
]}

机构：

[1] Biocon Bristol Myers Squibb R&D Ctr, Dept Discovery Synth, Biocon Pk,Plot 2&3,Bommasandra Jigani Rd, Bangalore 560099, India

[2] Bristol Myers Squibb Res & Early Dev, Small Mol Drug Discovery, 200 Cambridge Pk Dr, Cambridge, MA 02140 USA

[3] Bristol Myers Squibb, Small Mol Drug Discovery, POB 4000, Princeton, NJ 08543 USA

[4] Bristol Myers Squibb, 10300 Campus Point Dr Suite 100, San Diego, CA 92121 USA

来源：

TETRAHEDRON | 2024年 / 167卷

关键词：

Concise; Optically pure; (3R; 4R)-3-Methyl-4-aminopiperidines; Scalable; Stereoselective synthesis; DERIVATIVES; FENTANYL; ANALOGS;

D O I：

10.1016/j.tet.2024.134239

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An efficient, scalable and stereoselective synthesis of optically pure (3R,4R)-1-benzyl- and (3R,4R)-1-Boc-3methyl-4-aminopiperidines has been developed starting from commercially available N-benzyl-3-methyl-4piperidone. The synthesis employed chiral resolution of N-benzyl-3-methyl-4-piperidone, cis-selective reduction of a keto group, and subsequent Mitsunobu inversion of the resulting hydroxy group to install an amine with the desired trans-stereochemistry as the key steps. The method described herein demonstrated a competent route to the title compounds in a cost-effective, and scalable manner.

引用

页数：6

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