Dimethylformamide → 4-[2-Hydroxymethyl-4-phenyloxazol-5-yl]benzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

Deoxybenzoin (10 g, 51 mmol) was added to chlorosulfonic acid cooled to 0° C. (25 mL) and the reaction was warmed to room temperature for 4 hours. The solution was carefully poured into ice water, filtered and the aqueous layer was extracted with three 250 mL portions of dichloromethane. The combined organics were washed once with brine (75 mL) and stirred over ice-cold NH4OH (125 mL) for 16 hours. The dichloromethane layer was separated and washed consecutively with 1N HCl (2×75 mL), NaHCO3 (saturated) (75 mL) and brine (75 mL), dried over Na2SO4 and concentrated. The crude material (4.23 g) was suspended in acetic acid (75 mL) and HBr/HOAc solution (33 u/V% HBr in HOAc, 25 mL) and Br2 (0.79 mL, 15.4 mmol) was added. After 0.25 hours at room temperature the reaction was complete by TLC, and the reaction was concentrated to remove the acetic acid. The residue was dissolved in ethyl acetate (250 mL) and NaHSO3 (10%, 250 mL). The organics were washed with NaHCO3 (saturated) (75 mL) and brine (75 mL), dried over Na2SO4 and concentrated yielding a crude 4-sulfonamido-desylbromide which was used without purification. Glycolic acid mono sodium salt (1.55 g, 15.8 mmol) and the 4-sulfonamido-desylbromide were suspended in DMF (350 mL) and stirred at room temperature for 16 hours. The reaction was concentrated and the residue, along with ammonium acetate (2.31 g, 30 mmol) and acetic acid (25 mL), were heated to reflux for 3 hours. The reaction was concentrated to dryness. The residue was dissolved in ethyl acetate (250 mL)l, washed with water, NaHCO3 and brine, dried and concentrated. The crude product was chromatographed over SiO2, eluting with a gradient from 50%-75% ethyl acetate in hexane, to yield 4-[2-hydroxymethyl-4-phenyl-5-oxazolyl]benzenesulfonamide: 1H NMR (acetone-d6) 300 MHz δ 4.76 (m, 2H), 6.68 (s, 2H), 7.45 (m, 3H), 7.65 (m, 2H), 7.77 (d, J=6.8 Hz, 2H), 7.94 (d, J=8.7 Hz, 2H).

Provenance & Evidence