Tetrahydrofuran → Methyl 3-(5-bromothiophen-2-yl)-3-oxopropanoate

Participants

Reaction Conditions

Reaction Steps

To a 500 mL round bottom flask was added a suspension of sodium hydride (1.950 g, 48.76 mmol) in tetrahydrofuran (250.00 mL, 3082.3 mmol). Dimethyl carbonate (8.218 mL, 97.53 mmol) was added followed by 2-bromo-5-acetylthiophene (5.000 g, 24.382 mmol) which was added in portions. The reaction mixture was heated to 60° C. and allowed to stir for 18 hours. The reaction was cooled to ambient temperature and quenched by the dropwise addition of water (100.0 mL). The mixture was acidified to pH 2 with 6N HCl (8.00 mL) and extracted with diethyl ether (150.00 mL×3). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude material was split in half and dry loaded onto silica gel and then purified using a ISCO (40 g cartridge, gradient hexanes to 25% EtOAc over 30 min) to afford the title compound (5.547 g, 82%) as a brown oil. LC/MS (AA) ES+ 263, 265. 1H NMR (dmso-d6, 400 MHz): δ 7.87 (d, 1H), 7.45 (d, 1H), 4.13 (s, 2H), 3.65 (s, 3H).

Provenance & Evidence