Hydrochloric Acid → (2-Aminophenyl)(pyridin-4-yl)methanone

Participants

Reaction Conditions

Reaction Steps

4-Bromopyridine (10) (49.38 g, 0.254 mol, free based from the hydrochloride by partitioning between ether and saturated bicarbonate) and diethyl ether (200 mL) was added over 1 h to a cooled solution (−78° C.) of n-butyl lithium (0.381 mol of a 2.5 M solution in hexane) under argon. After 30 min at (−78° C.), magnesium bromide diethyl etherate (98.37 g, 0.381 mol) was added via a dry powder addition funnel. After 1 h at −78° C., the reaction mixture was transferred to a jacketed addition funnel at −50° C., the solution was added to a cooled solution (−50° C.) of anthranilonitrile (15.0 g, 0.127 mol) and benzene (400 mL) over 10 minutes. The reaction was allowed to warm to 23° C. After 16 h, the reaction was poured into 18% sulfuric acid (100 mL), and was digested for 1 h. The resultant mixture was extracted with ethyl acetate ((400 mL), washed with water (3×400 mL), and dried (MgSO4). After concentration in vacuo, the residue was purified by flash chromatography in a step gradient fashion (one liter methylene chloride; one liter ethyl acetate:methylene chloride 1:9; one liter ethyl acetate:methylene chloride 2:8; one liter ethyl acetate:methylene chloride 3:7; one liter ethyl acetate:methylene chloride 4:6) which afforded 4-(2-aminobenzoyl)pyridine (12) as a solid : Mass Spectrum (CI) 199 (MH+).

Provenance & Evidence