| 第 50 卷第 2 期 |  | Vol. 50 No. 2 | | 2020 年 4 月 | Apr 2020 |
|
所屬欄目：醫藥及中間體
1-叔丁氧羰基-（S）-2-羥甲基氮雜環(huán)丁烷的合成 |
| 胡 濤，朱曉鶴，朱云龍
（揚子江藥物研究院，藥物制劑新技術(shù)國家重點(diǎn)實(shí)驗室，江蘇 泰州 225321） |
| 摘 要：報道了一種合成（S）-2-羥甲基氮雜環(huán)丁烷的新方法，即以γ-丁內酯為起始原料，經(jīng)溴代開(kāi)環(huán)成2，4-二溴丁酸甲酯（2），然后與（S）-α-苯乙胺雙取代環(huán)化生成氮雜1-［（S）-1-苯乙基］-2-甲氧羰基氮雜環(huán)丁烷的兩種非對映異構體3a（2S，1′S）和3b（2R，1′S），經(jīng)柱層析分離，氫化鋁鋰還原成醇（4）后，氫解脫去（S）-1-苯乙基和引入Boc保護基生成標題化合物1-叔丁氧羰基-（S）-2-羥甲基氮雜環(huán)丁烷�？偣�4步反應，總收率為40%。1H NMR和MS表征確證了關(guān)鍵中間體和目標產(chǎn)物結構。 |
| 關(guān)鍵詞：γ-丁內酯；（S）-α-苯乙胺；非對映異構體；2（S）-羥甲基氮雜環(huán)丁烷 |
| 中圖分類(lèi)號：TQ463 文獻標識碼：A 文章編號：1009-9212（2020）02-0030-04 |
|
| Synthesis of 1-Boc-(S)-2-(hydroxymethyl)azetidine |
| HU Tao, ZHU Xiao-he，ZHU Yun-long
(Yangtze River Drug Research Institue, State Key Lab of Advanced Pharmaceutical Formulation with High Technology, Taizhou 225321, China) |
| Abstract：A novel synthetic approach of(S)-2-(hydroxymethyl)azetidine was described. Starting from γ-butyrolactone, the ring-opening bromization gave methyl 2,4-dibromobutanoate 2. The subsequent bis-substitution cyclization with (S)-α-phenylethanamine provided diastereoisomers 3a and 3b of (S)-methyl 1-((S)-1-phenylethyl)azetidine-2-carboxylate, which could be easily isolated by the column chromatography. The reduction into alcohol 4 with lithium aluminum hydride, followed by the hydrogenesis and Boc protection afforded the title compound (S)-tert-butyl 2-(hydroxymethyl)azetidine-1-carboxylate with an overall yields of 40%. The related compounds were confirmed by 1H NMR and MS. |
| Key words：γ-butyrolactone; (S)-α-phenylethanamine; diastereoisomers ; 2(S)-(hydroxymethyl)azetidine |
|
作者簡(jiǎn)介：胡 濤（1975-），男，河南信陽(yáng)人，高級工程師，主要從事小分子化學(xué)新藥的藥物化學(xué)研究（E-mail：hutao@haiyanpharma.com）。
|
收稿日期：2019-12-03
|
|