(1,1'-Biphenyl)-4-carboxylic acid → Ethyl 2-[(4-phenylphenyl)carbonylamino]acetate

Participants

Reaction Steps

To a stirred solution of biphenyl-4-carboxylic acid (10 g, 0.05044 mole) in DMF (50 mL), was added DIPEA (22.82 g, 0.176 mol), HOBt (7.496 g, 0.0554 mol) and EDCI.HCl (17.4 g, 0.09 mol) at ambient temperature. After 2 minutes glycine ethyl ester hydrochloride (8.45 g, 0.06 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was diluted with cold water and the resulting precipitate was isolated by filtration and dried to afford 14.26 g (99.8%) of [(biphenyl-4-carbonyl)-amino]-acetic acid ethyl ester. 1H NMR (DMSO-d6): δ9.0 (t, 1H), 8.0-7.9 (d, 2H), 7.84-7.7 (dd, 4H), 7.5 (t, 2H), 7.46-7.36 (m, 1H), 4.2-4.1 (q, 2H), 4.0 (d, 2H), 1.25 (t, 3H). To a stirred solution of [(biphenyl-4-carbonyl)-amino]-acetic acid ethyl ester (14.26 g, 0.05 mol) in a mixture of THF (60 mL), methanol (60 mL) and H2O (30 mL) was added LiOH.H2O (12.68 g, 0.3023 mol) and the resulting mixture was stirred at ambient temperature for 1 hour. The volatiles were then evaporated and the residue was acidified with 10% aqueous HCl solution. The resulting precipitate was isolated by filtration washed with water followed by hexane and dried to afford 12.8 g (99%) of [(biphenyl-4-carbonyl)-amino]-acetic acid. 1H NMR (DMSO-d6): δ 8.0-7.85 (m, 3H), 7.8-7.7 (m, 4H), 7.55-7.45 (t, 2H), 7.45-7.35 (t, 1H), 3.5 (d, 2H).

Provenance & Evidence