4-(Hydroxymethyl)phenyl pivalate

623-05-2

3282-30-2

59012-91-8

Procedure for the synthesis of 4-(hydroxymethyl)phenyl trimethyl acetate (Compound M1): to a stirred solution of 4-hydroxybenzyl alcohol (6.21 g, 50 mmol) in anhydrous THF (50 mL) was added triethylamine (10.43 mL, 75 mmol) under the protection of argon, followed by a slow dropwise addition of pivaloyl chloride (6.79 mL, 55 mmol) at room temperature. The reaction mixture was continued to be stirred at room temperature for 60 minutes. Upon completion of the reaction, the reaction was quenched by the addition of water (0.2 mL) and the mixture was allowed to stand overnight. Subsequently, the reaction mixture was diluted with EtOAc (~400 mL) and washed sequentially with saturated NaHCO3 solution (3 x 100 mL) and brine (100 mL). The organic phase was dried with Na2SO4, filtered and concentrated. The product was purified by rapid chromatography on a silica gel column (4 × 20 cm) (TLC conditions: Rf = 0.4, unfolding agent was ethyl acetate/hexane (4:6)), and ethyl acetate/hexane (4:6) was used as eluent. The fractions containing the pure product were combined, concentrated and dried under vacuum to give 7.75 g (74% yield) of the target compound in the form of a colorless oil.1H NMR (DMSO-d6): δ 7.35 (d, 2H, J = 8.6 Hz), 7.04 (d, 2H, J = 8.6 Hz), 5.22 (t, 1H), 4.50 (d, 2H), 1.31 (s, 9H).