tert-Butanol → Methyl 4-bromothiophene-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A biphasic mixture of 4-bromothiophene-2-carbaldehyde (13.2 g, 69.1 mmol, 1 equiv), sodium chlorite (9.40 g, 104 mmol, 1.50 equiv), sodium phosphate monobasic (9.53 g, 69.1 mmol, 1.00 equiv) in a mixture of t-BuOH (120 mL), 2-methyl-2-butene (20 mL), and water (50 mL) was stirred at 23° C. for 1 hour. More sodium chlorite 3.00 g, 33.2 mmol, 0.480 equiv) and a solution of sodium phosphate monobasic (3.00 g, 21.7 mmol, 0.315 equiv) in water (25 mL) were added. The resulting mixture was stirred for 1 hour, then concentrated. The residue was diluted with aqueous 0.1 N sodium hydroxide solution, and the resulting aqueous mixture was extracted with ethyl acetate (200 mL). The aqueous layer was then acidified to pH 2 with aqueous 1 N HCl solution and extracted with dichloromethane (3×100 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was dissolved in anhydrous methanol (600 mL) and concentrated sulfuric acid (4 mL) was added. The resulting solution was heated at reflux for 48 hours. The reaction mixture was concentrated, then carefully partitioned between aqueous saturated sodium bicarbonate solution (400 mL) and ethyl acetate (2×200 mL). The organic layer was dried over sodium sulfate and concentrated to give methyl 4-bromothiophene-2-carboxylate (5-1) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, 1H, J=1.5 Hz), 7.44 (d, 1H, J=1.5 Hz), 3.90 (s, 3H).

Provenance & Evidence