Ethyl chloroformate → 6-Chloro-5-(difluoromethyl)-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Participants

Reaction Conditions

Reaction Steps

A stirred solution of 5-chloro-4-(difluoromethyl)-N-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,2-benzenediamine (D98, 180 mg, 0.50 mmol) in tetrahydrofuran (8 ml) at room temperature under argon was treated with N,N-diisopropylethylamine (0.18 ml, 1.0 mmol) followed by ethyl chloroformate (65 mg, 0.60 mmol) and maintained for 1 hr. The solution was concentrated under vacuum and the residue dissolved in dimethylformamide (5 ml) and heated at 150° C. under argon for 1.5 hrs. The solution was concentrated under vacuum and the residue treated with 10% Na2CO3 solution and extracted with ethyl acetate. The extract was dried and concentrated under vacuum to leave an orange solid, which was washed with diethyl ether. The remaining solid was converted to its HCl salt, which was again washed with diethyl ether to afford the HCl salt of the title compound as a pale yellow solid (92 mg, 47%).

Provenance & Evidence