酒石酸阿福特罗的合成工艺研究

Study on Synthesis Process of Arformoterol Tartrate

以3′-硝基-4′-苄氧基-2-溴苯乙酮(2)为起始原料,经手性不对称还原、硝基还原和甲酰化、分子内环合和缩合、脱苄基保护基和精制制得酒石酸阿福特罗。不对称还原体系为硼烷二甲硫醚/(1 R,2 S)-1-氨基-2-茚醇,纯化溶剂为甲苯和异丙醚。硝基的还原体系为10%Pt/C/Me_(2)S,酰化剂为甲酸-乙酸酐混酐。4的分子内环合温度为30~35℃,缩合温度为110~120℃,脱保护压力为1.2~1.5 MPa,纯化溶剂为乙醇/纯化水。改进的制备方法克服了文献所报道的制备工艺的一些缺点。

Arformoterol Tartrate was synthesized from 1-(4-(Benzyloxy)-3-nitrophenyl)-2-bromoethanone as the start material via chiral asymmetry reduction,nitro-group reduction and formylation,intramolecular cyclization and condensation,debenzyl protective group and purification.The reducing agent of borane dimethyl sulfide complex anf(1 R,2 S)-1-amino-2,3-dihydro-1 H-inden-2-ol was used in the synthesis of intermediate 3,and the purified solvent was toluene and isopropyl ether.The reducing agent of the nitro group was 10%Pt/C and dimethyl sulfide,the acylating agent was formic acid-acetic anhydride mixed anhydride.The intramolecule-ar cyclic binding temperature of 4 was 30 to 35℃,the condensation temperature was 110 to 120℃,and the deprotection pressure was 1.2 to 1.5 MPa,the purified solvent was ethanol/purified water.Some drawbacks in the literatures were improved.