Chemical and Enzymatic Resolution of (R,S)-N-(tert-Butoxycarbonyl)-3-hydroxymethylpiperidine

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• 作者：Animesh Goswami ; Jeffrey M. Howell ; Edward Y. Hua ; K. David Mirfakhrae ; Maxime C. Soumeillant ; Shankar Swaminathan ; Xinhua Qian ; Fernando A. Quiroz ; Truc C. Vu ; Xuebao Wang ; Bin Zheng ; David R. Kronen
• 刊名：Organic Process Research & Development
• 出版年：2001
• 出版时间：July 2001
• 年：2001
• 卷：5
• 期：4
• 页码：415 - 420
• 全文大小：65K
• 年卷期：v.5,no.4(July 2001)
• ISSN：1520-586X

文摘

(S)-N-(tert-Butoxycarbonyl)-3-hydroxymethylpiperidine 1 wasmade from (R,S)-3-hydroxymethylpiperidine 2 via fractionalcrystallization of the corresponding L(-)-dibenzoyl tartaratesalt 3 followed by hydrolysis and acylation. Lipase fromPseudomonas cepacia was found to be the best enzyme for thestereospecific resolution of (R,S)-N-(tert-butoxycarbonyl)-3-hydroxymethylpiperidine 4. (S)-N-(tert-Butoxycarbonyl)-3-hydroxymethylpiperidine 1 was obtained in 16% yield and >95%enantiomeric excess (ee) by hydrolysis of (R,S)-acetate 5 bylipase PS from Pseudomonas cepacia. Lipase PS-catalyzedesterification of the (R,S)-N-(tert-butoxycarbonyl)-3-hydroxymethylpiperidine 4 with succinic anhydride provided the S-hemisuccinate ester 6, which could be easily separated andhydrolyzed by base to the (S)-N-(tert-butoxycarbonyl)-3-hydroxymethylpiperidine 1. The yield and ee could be improvedgreatly by repetition of the process. Using the repeated esterification procedure (S)-N-(tert-butoxycarbonyl)-3-hydroxymethylpiperidine 1 was obtained in 32% yield (maximum theoreticalyield 50%) and 98.9% ee.