摘要
(S)-1-(2-氯乙酰基)吡咯烷-2-甲腈(1)是合成降血糖药物维达列汀的重要中间体。本文研究了两种合成化合物1的方法。路线1:以L-脯氨酸为起始原料,经酰化、氨基化、脱水三步反应,总收率40.9%。路线2:以Boc-L-脯氨酸为起始原料,经氨基化、脱保护基、酰化、脱水四步反应,总收率37.2%。所有中间体结构均经过1H-NMR确认。这两条路线均原料易得、步骤较少、操作方便且收率较高,适合工业化生产。
(S)-1-(2-chloro-acetyl) pyrrolidine-2-carbonitrile (1) is a key intermediate for preparing vildagliptin. Compound 1 was synthesized by two routes with different starting materials. Route 1 was starting with L-proline through acylation, amination, dehydration to afford the target compound, with an overall yield of 40.9 %. Route 2 was starting with Boc-L-proline through amination, de-Boc protection, acylation, dehydration to afford the target compound, with an overall yield of 37.2 %. All compounds were confirmed through 1H-NMR. These routes were suitable for industrial production since they have a lot of advantages such as readily available materials, fewer steps, simple operations and high yields.
