3-(4-Hydroxyphenyl)hex-4-ynoic acid (23.5 g, 115 mmol) was dissolved in acetone (230 mL) and potassium bicarbonate (11.5 g, 115 mmol) was added and stirred for 15 minutes. Subsequently, iodomethane (5 mL, 80 mmol) was added and the reaction mixture was stirred at 40 °C overnight. Iodomethane (3 mL, 48 mmol) was added again and the reaction continued to be heated for 24 hours. After completion of the reaction, the insoluble material was removed by filtration and washed with acetone. The filtrate was concentrated to an oil and purified by silica gel column chromatography using a dichloromethane solution containing 2.5% methanol as eluent. Methyl 3-(4-hydroxyphenyl)hex-4-ynoate (21.5 g, 85% yield) was finally obtained as a light yellow oil.1H NMR (500 MHz, acetone-d6) δ: 8.2 (br s, 1H), 7.20 (d, J=9.5 Hz, 2H), 6.77 (d, J=9.0 Hz, 2H), 3.98 (m, 1H), 3.60 (s, 3H), 2.65 (m, 2H), 1.78 (d, J=2.5Hz, 3H).MS (ESI) m/e: 219.1 (M+H)+, 241 (M+Na)+.
