（S）\|N,N\|二甲基\|3\|羟基（2\|噻吩基）丙胺的合成

为了解决（S）\|N,N\|二甲基\|3\|羟基（2\|噻吩基）丙胺合成工艺中操作较复杂，产率低的问题，以2\|乙酰噻吩、二甲胺盐酸盐、多聚甲醛为起始原料，经曼尼希反应、硼氢化钠还原和S\|(+)\|扁桃酸拆分合成（S）\|N,N\|二甲基\|3\|羟基（2\|噻吩基）丙胺.采用单因素分析方法考察了浓盐酸的用量、投料比、反应时间对产物收率的影响，得到各步反应的最佳工艺条件:曼尼希反应的最佳投料比为n(2\|乙酰噻吩)∶n(浓盐酸的用量)=15∶1，产物收率可达90.6%；还原反应在25 ℃下，投料比为n(3\|二甲胺基\|1\|(2\|噻吩基)\|1\|丙酮盐酸盐)∶n(硼氢化钠)=1∶0.55，反应6 h时效果最佳；拆分反应的最佳条件是反应温度85 ℃，反应45 min.优化后反应的总收率可达60.3%，目标产物经核磁共振氢谱、质谱确认.该合成工艺原料便宜易得，反应条件温和，工艺操作简便适合工业化生产.

Synthesis of (S)\|N,N\|Dimethyl\|3\|(2\|thienyl)\|3\|Hydroxyp\|ropanamine

To solve the problems of complicated production process conditions,low production rate of (S)\|N,N\|Dimethyl\|3\|(2\|thienyl)\|3\|hydroxypropanamine,2\|acetyl thiophene，dimethylamine hydrochloride and paraformaldehyde were applied as raw materials to prepare (S)\|N,N\|Dimethyl\|3\|(2\|thienyl)\|3\|hydroxypropanamine through Mannich，reduction and resolution reaction. The influence of concentrated hydrochloric acid dosage，feed ratio，reaction time on the product yield was studied by single factor analysis method.The yield is 90.6% when the molar ratio of (2\| acetyl thiophene)∶(concentrated hydrochloric) is 15∶1 in the Mannich reaction.The optimum conditions of the reduction reaction are demonstrated at 25 ℃ for 6h with molar ratio of (3\|Dimethylamino\|1\|(2\|thienyl)\|1\|propanone hydrochloride)∶(Sodium borohydride)=1∶0.55. The best condition of resolution reaction is at 85 ℃ for 45 min.The total yield is 60.3% after optimum reaction and the target compound was elucidated by nuclear magnetic resonance spectrum spectroscopy and mass spectrum. This method is feasible for industry with low cost,mild condition,easy operation.