Sodium amide → 3-(2-Methoxypyridin-4-yl)propanoic acid

Participants

Reaction Conditions

Reaction Steps

Sodamide (4 g, 103 mmol) and 2-methoxy-4-methylpyridine (9 g, 73 mmol) in liquid ammonia (150 mL) was stirred for 30 min at −50° C. The dark orange mixture was carefully treated with sodium 2-chloroacetate (9 g, 78 mmol). After 1.5 hours a second portion of sodium 2-chloroacetate (8 g, 69 mmol) was added. After a total reaction time of 3.5 hours, the reaction mixture was treated with ammonium chloride (13 g, 245 mmol). Ammonia was allowed to evaporate and the solid residue was treated with water (200 mL) and extracted with DCM (50 mL×3). The aqueous layer was acidified to pH=1 with concentrated hydrochloric acid and then extracted with ethyl acetate (3×50 mL). The aqueous layer was basified to pH 4.5 with 40% w/v aqueous sodium hydroxide, then cooled to 0-5° C., and stirred at this temperature for 2 hours. The mixture was filtered under reduced pressure and the filter cake was washed with water (5 mL), and dried to give 3-(2-methoxypyridin-4-yl)propanoic acid (3.2 g, 24%) as a white solid. LC-MS: 182 [M+H]+, tR=1.10 min.

Provenance & Evidence