2-Acetylthiophene → Ethyl 3-oxo-3-(thiophen-2-yl)propanoate

Participants

Reaction Steps

To a suspension of sodium hydride (7.13 g, 178 mmol, 60% in mineral oil) in benzene (100 mL) was added diethyl carbonate (14.0 g, 118 mmol). The mixture was heated to reflux and a solution of 2-acetylthiophene (7.48 g, 59.4 mmol) in benzene (20 mL) was added dropwise over 1 hour. When addition was complete, the mixture was refluxed for a further 3 hours, after which hydrogen evolution had ceased. The reaction was quenched with acetic acid (15 mL) and then with ice-cold water (45 mL). The organic phase was separated, the aqueous layer was extracted with benzene and the combined extracts were washed with cold water, dried (Na2SO4) and concentrated under reduced pressure. The residue was distilled under high vacuum to give 36 (8.15 g, 69%) as a colorless oil: by 130° C. (0.3 torr): IR (neat) 2925, 2848, 1742, 1669, 1459, 1373, 1030, 851, 723 cm−1; 1H NMR (400 MHz, CHCl3) δ 1.28 (t, 3H, J=7 Hz), 3.93 (s, 2H), 4.25 (q, J=Hz, 2H), 7.16 (m, 1H), 7.71-7.76 (m, 2H); 13C NMR (300 MHz, CDCl3) δ 14.1, 46.5, 61.6, 128.3, 133.2, 134.9, 142.4, 167.0, 185.2: HRMS (EI) m/z 198.0349 (calcd for C9H10O3S 198.0351).

Provenance & Evidence