Toluene → HCID 70818683, compound

Participants

Reaction Steps

A solution of 4-methyl-2,3-dihydro-1-benzofuran-3-one (26c) (200 mg, 1.35 mmol) in ethyl glyoxylate 50% in toluene (0.40 mL, 2.02 mmol) was heated at 100° C. for 16 hours. The mixture was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate: 95/5 to 80/20) to provide ethyl 2-hydroxy-2-(4-methyl-3-oxo-2,3-dihydro-1-benzofuran-2-yl)acetate (26d) (200 mg, 0.8 mmol) which was dissolved in a mixture of cyclohexane (2 mL) and dichloromethane (0.5 mL) before adding silver oxide (560 mg, 2.4 mmol) and tert-butyl bromide (0.54 mL, 4.8 mmol). The mixture was stirred at room temperature for 60 hours, with addition of silver oxide and tert-butyl bromide every hour of working day until the reaction stopped evolution. The mixture was filtered over Celite®, and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 90/10) to provide ethyl 2-(tert-butoxy)-2-(4-methyl-3-oxo-2,3-dihydro-1-benzofuran-2-yl)acetate (26e) (73 mg, 0.238 mmol) which was dissolved in a mixture of dimethylformamide (1.5 mL) and tetrahydrofuran (0.2 mL) under argon atmosphere. This mixture was cooled at −78° C. and a 1.0 M solution of potassium t-butoxide in tetrahydrofuran (0.26 mL, 0.262 mmol) was added. After 1 hour stirring at −78° C., a solution of N-phenyl-bis(trifluoromethanesulfonimide) (98 mg, 0.274 mmol) in dimethylformamide (0.07 mL) and tetrahydrofuran (0.3 mL) was slowly added and the mixture was further stirred at the same temperature for 90 minutes. The reaction was quenched by addition of saturated sodium carbonate solution (5 mL) and the mixture was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative TLC (cyclohexane/ethyl acetate 80/20) to provide ethyl 2-(tert-butoxy)-2-{4-methyl-3-[(trifluoromethane)sulfonyloxy]-1-benzofuran-2-yl}acetate (26f) (60 mg, 0.137 mmol, 17% over 3 steps).

Provenance & Evidence