1,4-Butanediol → 4-[3-(2-Methoxyphenylsulfonyloxy)-5-methylphenoxy]butanol

Participants

Reaction Conditions

Reaction Steps

A solution of 3-(2-methoxyphenylsulfonyloxy)-5-methylphenol (177 mg, 0.60 mmol, as prepared in step b of example 8), 1,4-butanediol (0.53 mL, 6.0 mmol), triphenylphosphine (316 mg, 1.2 mmol), and anhydrous tetrahydrofuran (4 mL) was cooled to 0° C., then diethyl azodicarboxylate (0.20 mL, 1.2 mmol) was added dropwise over 5 minutes. The solution was stirred at 0° C. for 15 min and then at ambient temperature overnight. Additional triphenylphosphine (3×320 mg) and diethyl azodicarboxylate (3×0.20 mL) were added over the next 3 days. The mixture was filtered, and the filtrate was concentrated. The residue was triturated with 40% ethyl acetate in hexane, then the mixture was filtered and the filtrate was concentrated. Crude product was purified by flash column chromatography through silica gel (40% to 70% ethyl acetate in hexane, then 0% to 2% acetone in dichloromethane in a separate chromatographic separation) to give the title compound as a colorless oil (85.4 mg, 39%). 1H-NMR (300 MHz, CDCl3) δ 7.83 (dd, 1H, J=1.8, 7.9 Hz), 7.61 (ddd, 1H, J=1.7, 7.4, 8.4 Hz), 7.08 (d, 1H, J=8 Hz), 6.99-7.04 (m, 1H), 6.57 (br s, 1H), 6.50 (br s, 1H), 6.44 (t, 1H, J=2.2 Hz), 4.02 (s, 3H), 3.88 (t, 2H, J=6.0 Hz), 3.70 (q, 2H, J=6 Hz), 2.24 (s, 3H), 1.65-1.87 (m, 4H), 1.45 (t, 1H, J=6 Hz).

Provenance & Evidence