Sulfuric Acid → (6-Bromo-benzo[b]thiophen-2-yl)-acetic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

To a 0° C. solution of (6-bromo-benzo[b]thiophen-2-yl)-acetaldehyde (2.21 g; 8.66 mmol) in t-butyl alcohol (50 mL; 526.36 mmoles; 50.00 mL; 39.015 g) and 2-methyl-2-butene (20 mL; 188 mmol) is added a solution of sodium chlorite (6.27 g; 69.3 mmol) in water (20 mL) and a solution of sodium phosphate monobasic (4.20 g; 34.6 mmol) in water (10 mL). The reaction mixture is stirred at 0° C. for 12 hours while warming to room temperature. The mixture is extracted with EtOAc (50 mL×2). The combined organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is dissolved in methanol (30 mL). Sulfuric acid (1.0 mL; 18.8 mmol) is added and the mixture is stirred at 95° C. for 4 hours. The mixture is neutralized with aqueous NaHCO3 and concentrated under reduced pressure. The residual aqueous mixture is extracted with EtOAc (50 mL×2). The combined organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is purified via flash chromatography eluting with 20% EtOAc/Hexanes. The appropriate fractions are combined and concentrated under reduced pressure to afford the title compound (1.51 g, 61%). ES/MS m/e (M+18):303.8; (M−1):284.7

Provenance & Evidence