A process for the preparation of N-[(6-chloropyridin-3-yl)methyl]-2,2-difluoroethanamine using 2,2-difluoroethanamine hydrochloride controlled release base
By continuously adding 2,2-difluoroethylamine hydrochloride and sodium hydroxide aqueous solution within a specific time window in an acetonitrile medium, the problems of secondary alkylation and CCMP hydrolysis in the prior art were solved, and the preparation of N-[(6-chloropyridin-3-yl)methyl]-2,2-difluoroethylamine with high yield and low impurities was achieved.
Patent Information
- Application Number
- CN202610600456.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-04-30
- Publication Date
- 2026-07-17
AI Technical Summary
In the preparation of N-[(6-chloropyridin-3-yl)methyl]-2,2-difluoroethylamine, it is difficult to simultaneously suppress the secondary alkylation and CCMP hydrolysis side reactions at amine dosages close to stoichiometry, resulting in increased impurities.
Using 2,2-difluoroethylamine hydrochloride as the starting amine source, sodium hydroxide aqueous solution was continuously added in acetonitrile medium through a specific time window to control the concentration of free 2,2-difluoroethylamine and avoid excessively high local peaks. Combined with online monitoring and control of the feeding rate, high yield of the target intermediate and low impurity generation were achieved.
With amine dosage close to stoichiometry, the target intermediate analytical yield is obtained at a rate of not less than 90%, and secondary alkylation impurities are controlled at a low level, reducing intermediate separation and purification steps.
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Figure CN122404247A_ABST