A new and efficient method for the synthesis of rocuronium bromide

• 作 者: Xue-Ying Wu Yao-Ling Wang Li Hai Ping Gong Yong Wu
• 机 构: Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Phar
• 出 处: Chinese Chemical Letters
• 发表日期: 2017年02期
• 关键词: bromide pyrrolidine remove epoxide currently preparing steps systematically intr

Rocuronium bromide has been used as an aminosteroid non-depolarizing neuromuscular blocker and muscle relaxant.In this work,a new and efficient route for preparing a key intermediate 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androstan-3α,17β-diol(6) was developed through a ring-opening of epoxide followed by introducing and pyrrolidine.Compound 6 can easily provide rocuronium bromide and the overall yield of compound 6 in 5 steps increased to 57.8%,which was higher than currently reported methods.Extraordinarily,this method would avoid the generation of disubstituted impurities E and F which are difficult to remove.

Rocuronium bromide has been used as an aminosteroid non-depolarizing neuromuscular blocker and muscle relaxant. In this work, a new and efficient route for preparing a key intermediate 2β- (4-morpholinyl) -16β- (1-pyrrolidinyl) -5α-androstan -3α, 17β-diol (6) was developed through a ring-opening of epoxide followed by introducing and pyrrolidine. Compound 6 can easily provide rocuronium bromide and the overall yield of compound 6 in 5 steps increased to 57.8%, which was higher than currently reported methods.Extraordinarily, this method would avoid the generation of disubstituted impurities E and F which are difficult to remove.