溴甲纳曲酮的合成

Synthesis of Methylnaltrexone Bromide

盐酸纳曲酮与乙二醇缩合、叔丁基二甲基氯硅烷保护,再与碘甲烷进行N-甲基化反应得(R)-3-[(叔丁基二甲基硅基)氧基]-17-环丙甲基-4,5a-环氧-14-羟基-6-(1,3-二氧戊烷-2-基)-N-甲基吗啡喃碘化物,再经氢溴酸水解、溴离子交换得溴甲纳曲酮,总收率53%,HPL,C纯度大于99%。

Methylnaltrexone bromide was synthesized from naltrexone hydrochloride via condensation with ethylene glycol, etherification with t-butyldimethylchlorosilane and methylation with methyl iodide to give （R）-3-[ （t- butyldimethylsilyl） oxy] - 17-cyclopropylmethyl-4,5 a-epoxy- 14-hydroxy-6- （1,3-dioxolane-2-yl） -N-methylmorphinanium iodide, which was subjected to hydrolysis with hydrobromic acid, ion exchange with bromide anion exchange resin. The overall yield was about 53 % and HPLC purity was more than 99%.