Ammonium Chloride → Methyl 2-[3-(4-methoxymethylbenzyl)phenyl acetamido]-4-chlorobenzoate

Participants

Reaction Conditions

Reaction Steps

The bromobenzylmethyl ether (2.28 g, 11.35 mmol) was dissolved in anhydrous ether (40 ml) and cooled to -78° C. with stirring under nitrogen. tert-Butyllithium (13.4 ml of a 1.7M solution in pentane, 22.7 mmol) was added dropwise over 5 mins, and stirring continued for 45 mins. This mixture was then cannulated into a suspension of pentynyl copper (1.48 g, 11.35 mmol) in anhydrous ether (40 ml) at -78° C. and allowed to warm to -40° C., with stirring under nitrogen. Light was excluded with aluminium foil. After 15 mins methyl 2-(3-bromomethylphenylacetamido)-4-chlorobenzoate (1.5 g, 3.78 mmol) was added as a solution in anhydrous THF (10 ml). The mixture was swirled manually as necessary. After stirring at -40° C. for 1.5 hours, the reaction was allowed to warm to room temperature and stirred for a further 1 hour. Saturated ammonium chloride solution was added and the mixture filtered through celite to remove copper residues. The organic layer was separated and washed with water and brine before drying (Na2SO4) and evaporating in vacuo to give a yellow oil. This was purified by flash chromatography eluting with 15% ethyl acetate in hexane to give methyl 2-[3-(4-methoxymethylbenzyl)phenyl acetamido]-4-chlorobenzoate as a clear colourless oil (0.81 g, 1.85 mmol); δH (360 MHz, CDCl3) 3.36 (3H, s, CH2OCH3), 3.71 (2H, s, NHCOCH2), 3.84 (3H, s, COOCH3), 3.99 (2H, s, ArCH2Ar), 4.41 (2H, s, ArCH2O), 7.03 (1H, dd, J 8.6 and 2.1 Hz, 5-H), 7.10(1H, d, J 7.5 Hz, Ar--H), 7.16-7.30 (7H, m, Ar--H), 7.91(1H, d, J 8.6 Hz, 6-H), 8.81(1H, d, J 2.1 Hz, 3-H), 11.06(1H, br s, NH); m/z (EI+) 437 (M+).

Provenance & Evidence