阿达帕林的合成工艺研究

Study on Synthetic Process of Adapalene

以1-金刚烷醇、4-溴苯酚为原料,在浓硫酸催化下制得2-(1-金刚烷基)-4-溴苯酚,产物再用硫酸二甲酯甲基化得到2-(1-金刚烷基)-4-溴苯甲醚,2-(1-金刚烷基)-4-溴苯甲醚的格氏化产物再与6-溴-2-萘甲酸甲酯反应,制得6-〔3-(1-金刚烷基)-4-甲氧基苯基〕-2-萘甲酸甲酯,该产品在氢氧化钠作用下皂化水解得阿达帕林,反应总收率达到73%。

Adapalene is synthesized from 4 - bromophenol and 1 - adamantanol by a four - step reaction, First,4 - bromophenol is alkylated by 1 - adamantanol from 2 - （ 1 - adamantyl） - 4 - bromophnol, the compound 2 - （1 -adamantyl） -4 -bromophenol is reacted with dimethylsuffate to give 2 - （1 -adama- ntyl） -4 - bromoanisole, compound 2 - （ 1 - adamantyl） -4 - bromoanisole is condensed to 6 - bromo - 2 - naphthoic acid methyl ester to produce 6 - [ 3 - （ 1 - adamantyl） - 4 - methoxyphenyl ] - 2 - naph- thoate. Last, saponification of compound 6 - [ 3 - （ 1 - adamantyl） - 4 - methoxyphenyl ] - 2 - naphthoate methanol afforded adapalene, the total yield is 73%.