[(2,2-difluoro-ethylcarbamoyl)-methyl]-carbamic acid tert-butyl ester synthesis

Yield:-

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine;HATU in dichloromethane at 20; for 1 h;

Steps:

244.M

M) Synthesis of [(2,2-difluoro-ethylcarbamoyl)-methyl]-carbamic acid /er/-butyl esterN) To a solution of compound tert-butoxycarbonylamino acetic acid (19.6 g,0.1 mol) in dichloromethane (200 mL) is added N,N-diisopropylethylamine (13.2 g, 0.1 mol), 2,2-difluoroethylamine (10 g, 0.1 mol) and HATU (23 g, 0.17 mol), after the addition the mixture is stirred at room temperature for 1 hour. After being detected by TLC and LCMS, the reaction mixture is diluted with dichloromethane, then the solution is washed with water and brine, dried over anhydrous Na₂S0₄, filtered, concentrated and the residue is dried in vacuum to give 30 g crude product, which is used directly in next step.

References:

WO2012/155676,2012,A1 Location in patent:Page/Page column 76-77