恩曲他滨的合成

Synthesis of Emtricitabine

[（2R,5S）-（5-氟胞嘧啶-1-基）-1,3-氧硫环戊烷-2-羧酸 基酯（6）经硼氢化钠还原后,用盐酸除去剩余硼氢化钠,蒸除大部分乙醇,甲苯洗涤除去副产物薄荷醇,加入苯甲酸反应2 h,过滤得苯甲酸恩曲他滨,与三乙胺及乙酸乙酯混合,15-30℃搅拌反应4h,抽滤,即可得到高纯度的抗病毒药恩曲他滨,总收率72.2%（以6计）。

（2R,5S）-5-（4-Amino-5-fluoro-2-oxo-1（2H）-pyrimidinyl）-1,3-oxathiolane-2-carboxylic acid （1R,2S,5R）-5-methyl-2-（1-methylethyl）cyclohexyl ester（6） was reduced with sodium borohydride, removed excess sodium borohydride with hydrochloric acid, pressure distillation to remove most of the ethanol, washed with toluene to remove the byproducts menthol, the benzoic acid was added for 2 hours, and then filtered to give the new compound benzoic acid emtricitabine. Benzoic acid emtricitabine mixed with triethylamine and ethyl acetate, stirred at 15-30 ℃ for 4 h, followed by filtration to give high purity emtricitabine with an overall yield of 72.2%（based on 6）.