A Practical Kilogram-Scale Process to a Milnacipran Analogue, N,N-Diallyl (1R, 2R)-2-(Aminomethyl)-1-(2-thienyl)cyclopropanecarboxamide

作者：Li, Chen; Li, Bin-Feng^*; Chen, Jian-Ge; Sun, Tao; Chen, Zhenming

来源：Organic Process Research & Development, 2012, 16(12): 2021-2024.

DOI：10.1021/op3001542

• DERIVATIVES
• INHIBITORS
• SEROTONIN
• MOIETY

A robust chemical process to produce N,N-diallyl (1R,2R)-2-(aminomethyl)-1-(2-thienyl)-cyclopropanecarboxamide (2) has been developed and optimized. This unique process, employing the MsCl/NaN3 and Zn/NH4Cl system, overcomes many pitfalls of the literature reported processes, which mostly use chromatographic purification and catalytic hydrogenation with Pd/C. In addition, this novel process overcomes the safety concern with handling amide azide (8), as demonstrated by the results of the drop weight test and differential scanning calorimetry (DSC). This process has been successfully scaled-up to prepare several multikilogram batches of the target compound with overall yields of 80%, which is 15 times higher than those of reported procedures.

• 出版日期2012-12
• 单位杭州师范大学