(R)-3-氨基-3,4-二氢-1-甲氧基喹啉-2(1H)-酮的合成

Synthesis of(R)-3-amino-3,4-dihydro-1-methoxyquinolin-2(1H)-one

首先,以D-苯丙氨酸和二碳酸二叔丁酯为起始原料,经过Boc氨基保护合成N-叔丁氧羰基苯丙氨酸;然后N-叔丁氧羰基苯丙氨酸在甲氧氨盐酸盐的作用下生成缩合物2-(N-叔丁氧羰基)-N-甲氧基-3-苯丙酰胺;然后缩合物在催化剂二(三氟乙酸)碘苯的作用下成环生成3-(N-叔丁氧羰基)-3,4-二氢-1-甲氧基喹啉-2(1H)-酮;最后后者经过脱保护合成目标产物。该方法具有操作简单、成本低等优点,四步总收率15.1%,产物经过1H-NMR和MS确认。

N-(tert-butoxycarbonyl)-R-phenylalan was synthesized by D-phenylalanine and two Di-tert-butyl dicarbonate.Then tert-butyl(R)-1-(methoxycarbamoyl)-2-phenylethylcarbamate was synthesized under methoxylamine hydrochloride.Taking[bis(trifluoroacetoxy)iodo]benzene as a kind of catalyst,tert-butyl(R)-1,2,3,4-tetrahydro-1-methoxy-2-oxoquinolin-3-ylcarbamate was synthesized by tert-butyl(R)-1-(methoxycarbamoyl)-2-phenylethylcarbamate.Last,targete compound was synthesized by tert-butyl(R)-1,2,3,4-tetrahydro-1-methoxy-2-oxoquinolin-3-ylcarbamate.During the above four steps,the total yield was about 15.1%.The process was simple,manipulation easily,with low cost.The structure of the target compound and Intermediates were confirmed by MS and 1 H-NMR.