反应详情

温度

23 °C

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+).

1. customby partitioning between ether and saturated bicarbonate) and diethyl ether (200 mL)
2. additionwas 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
3. customthe reaction mixture was transferred to a jacketed addition funnel at −50° C.
4. waitAfter 16 h
5. waitwas digested for 1 h
6. extractionThe resultant mixture was extracted with ethyl acetate ((400 mL)
7. washwashed with water (3×400 mL)
8. dry with materialdried (MgSO4)
9. concentrationAfter concentration in vacuo
10. customthe 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