Hydrochloric Acid → Ethyl 4-(3-chlorophenyl)-2,4-dioxobutanoate

Participants

Reaction Steps

To an ice-cold solution of 1-(3-chlorophenyl)ethanone (16.79 mL, 129 mmol) and diethyl oxalate (18.05 mL, 136 mmol) in DMF (78.0 mL) was added, portionwise over 30 min., NaH (6.09 g, 155 mmol, 60% dispersion in mineral oil) and the resultant mixture was stirred at that temperature for 20 min. and then at room temperature for 16 h. The reaction mixture was diluted with water and acidified to pH=4-5 with 1N aq. HCl. The mixture was further diluted with copious amounts of water. The aq. layer was extracted with EtOAc (4×100 mL) and the combined organic layer was washed with water, brine, dried over anhydrous MgSO4, filtered and the filtrate was concentrated under reduced pressure to provide a crude residue. It was purified by silica gel chromatography (220 g REDISEP® column, eluting with a 0 to 15% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate A1C (27.1 g, 84%) as a solid. MS(ES): m/z=277.10 [M+Na]+; 1H NMR (400 MHz, chloroform-d) δ ppm 7.99 (t, J=1.8 Hz, 1H), 7.95-7.86 (m, 1H), 7.60 (ddd, J=8.0, 2.1, 1.0 Hz, 1H), 7.48 (t, J=7.9 Hz, 1H), 7.06 (s, 1H), 4.43 (q, J=7.3 Hz, 2H), 1.44 (t, J=7.2 Hz, 3H).

Provenance & Evidence