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
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.
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页数:6
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