Acetic Anhydride → 4-(3-Acetamido-4-methylphenyl)-4-oxobutanoic acid

Participants

Reaction Steps

10% Pd/C (100 g) was added to a solution of 4-(4-methyl-3-nitrophenyl)-4-oxobutanoic acid (73) (3.40 kg, 14.3 mol) and EtOAc (20 L) in 40 L Parr reactor. Acetic anhydride (2.40 L, 25.4 mol) was added. The mixture was stirred under about 5 bar H2 atmosphere overnight. The reaction was concentrated under reduced pressure. To the resulting grey solid was added EtOH (14 L) and H2SO4 (˜35 mL). The mixture was stirred in the 40 L Parr vessel under about 5 bar H2 pressure overnight at rt. The reaction mixture was poured into 2 N aqueous NaOH (35 L), stirred overnight at rt, and then filtered through of Celite® rinsing with water. The filtrate and washings were combined and concentrated under reduced pressure to remove EtOH. The aqueous residue was washed with tert-butyl methyl ether (7 L). The aqueous layer was acidified with 2 N aq. HCl. The precipitate was collected by filtration rinsing with water (2×14 L) and dried to afford 4-(3-acetamido-4-methylphenyl)-4-oxobutanoic acid (74) (2.70 kg, 76% yield). 1H NMR (300 MHz, DMSO): δ 12.03 (s, 1H), 9.25 (s, 1H), 7.50 (s, 1H), 7.30 (d, J=7.6 Hz, 2H), 6.88 (d, J=7.6 Hz, 2H), 2.56 (m, 2H), 2.28 (m, 2H), 2.16 (s, 3H), 2.04 (s, 3H), 1.74 (m, 2H).

Provenance & Evidence