Dabigatran Etexilate iMpurity I synthesis

Yield:-

Reaction Conditions:

with sodium hydroxide in dichloromethane at 20; for 4 h;

Steps:

1.1 (1) Preparation of dabigatran intermediate condensate oily substance:
To the reaction flask, add 21.2 g (0.10 mol) of p-aminobenzamidine dihydrochloride (II), 150 ml of dichloromethane. Add 80 ml of 15% (0.12 mol) solution of sodium hydroxide at a controlled temperature of 20 deg.C. Add dropwise 16.5g (0.1 mol) n-hexyl chloroformate (III). React for 4h. The aqueous layer was separated and the dichloromethane was distilled off to obtain 26.4 g of an oily product of the condensate (I).

References:

Shandong Xinhua Pharmaceutical Co., Ltd.;Di, Jisheng;Zhao, Bin;Zheng, Zhonghui;Xu, Ling;Li, Chengpeng CN105732433, 2016, A Location in patent:Paragraph 0016; 0017