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目的确定并优化曲司氯铵的合成工艺。方法以α-去甲托品醇(2)为原料,经与氯甲酸乙酯发生甲酰化反应制得N-乙氧羰基托品醇(3),3在二环己基碳二亚胺和4-二甲氨基吡啶的作用下与二苯羟乙酸发生酯化反应得到N-乙氧羰基二苯羟乙酸托品酯(4),4经甲酸铵/钯-炭催化氢转移还原体系去除乙氧羰基得到二苯羟乙酸去甲托品酯(5),5与1,4-二氯丁烷缩合成环即得目标物曲司氯铵。结果目标物的化学结构经1H-NM R谱确证且纯度达到99.5%(HPLC法)。结论该法操作简便,总收率为52%(以α-去甲托品醇计),适合工业化生产。
Objective To determine and optimize the synthesis of tartrimonium chloride. Methods N-Ethoxycarbonyltropine alcohol (3) was obtained by the formylation reaction of α-nortropyltropin (2) with ethyl chloroformate, and the reaction was carried out in the presence of dicyclohexylcarbodiimide and 4-dimethylaminopyridine under the action of esterification with diphenylacetic acid to give N-ethoxycarbonyl diphenyl glycolate (4), 4 by ammonium formate / palladium-carbon catalytic hydrogen transfer reduction system to remove B Oxycarbonyl to give diphenyloxanilide (5), 5 and 1,4-dichlorobutane condensation ring to obtain the target song song chloride. Results The chemical structure of the target was confirmed by 1H-NMR and its purity was 99.5% (HPLC method). Conclusion The method is simple and convenient, the total yield of 52% (α-proprotentol dollars), suitable for industrial production.