Acetic Acid → 5-Dimethylaminophthalide

Participants

Reaction Steps

Sodium cyanoborohydride (8.42 g, 134 mmol) was added into a stirred suspension of 5-aminophthalide (5.0 g, 33.5 mmol) and 37% CH2O/H2O solution (24.9 mL, 335 mmol) in 120 mL of acetonitrile. The mixture was stirred at room temperature for 1 hour, cooled to 0 C and 120 mL of 10% aqueous acetic acid solution was added. The mixture was then stirred at room temperature for 1 hour, evaporated under low pressure until no acetonitrile remained. The resulting mixture was extracted with ethyl acetate (2×125 mL). The combined organic extracts were washed with saturated NaHCO3 solution (125 mL) and brine (125 mL), dried over Na2SO4 and evaporated to dryness to give a light brown solid, which was triturated with hot MeOH (10 mL) to give the title compound (3.9 g, 66%) as an off-white solid.

Provenance & Evidence