Citric Acid → 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Participants

Reaction Steps

DMF (0.014 mL, 0.176 mmol) and oxalyl chloride (2.316 mL, 26.5 mmol) were added to a solution of 6-chloro-5-iodonicotinic acid (5 g, 17.64 mmol) in DCM (80 mL) and the RM was stirred for 2 h at RT under a nitrogen atmosphere. The solvent was evaporated off under reduced pressure and the residue was dissolved in THF (60 mL). DIPEA (9.24 mL, 52.9 mmol) was added and the mixture was cooled down to 5° C., treated dropwise with a solution of 4-(trifluoro methoxy)aniline (2.62 mL, 19.40 mmol) in DCM (20 mL) and stirred min at 5° C. for 30 and at RT for 1 h. The solvent was off under reduced pressure and the residue was treated with aq. 10% citric acid (70 mL) and extracted with EtOAc. The combined extracts were washed with sat. aq. Na2CO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product was suspended in n-hexane, and filtered to afford the title compound as a beige solid. UPLC-MS (Condition 2) tR=1.22 min, 440.9/442.9 [M−H]−.

Provenance & Evidence