Lithium Hexamethyldisilazide → 3-Bromo-N-[4-(2-chloro-phenyl)-pyridin-3-yl]-N-methyl-5-trifluoromethyl-benzamide

Participants

Reaction Conditions

Reaction Steps

To a solution of [4-(2-chloro-phenyl)-pyridin-3-yl]-methyl-amine (300 mg, 1.37 mmol, prepared according to DE10008042) in THF (3 mL) was added dropwise lithium bis(trimethylsilyl)amide (1M solution in THF, 1.44 mL, 1.44 mmol) at −78° C. The reaction mixture was stirred for 10 minutes at −78° C. A solution of 3-bromo-5-trifluoromethyl-benzoyl chloride (prepared by stirring 3-bromo-5-(trifluoromethyl)benzoic acid (406 mg, 1.51 mmol, CAS RN 328-67-6) in thionylchloride (3 mL) at 100° C. for 1 hour. The reaction mixture was evaporated and the residue was dissolved in 5 mL toluene and concentrated under vacuum. This procedure was repeated three times to completely remove remainder of thionylchloride) in THF (3 mL) was added at −78° C. The reaction mixture was stirred for 1 hour at this temperature and then poured on 30 mL H2O and 30 mL EtOAc. The layers were separated and the aqueous layer extracted a second time with 30 mL EtOAc. The combined organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Yellow solid (265 mg, 41%). MS (TurboSpray): m/z=470.991 [M+H]+.

Provenance & Evidence