Carbon Dioxide → 4-Chloro-5-cyclopropylpicolinic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of N,N-Dimethylethanolamine (CAN 108-01-0, 1.89 g, 2.13 ml, 21.2 mmol) in dry Hexane (40 ml) under an argon atmosphere at −15° C. was slowly added BuLi 1.6M in Hexane (26.4 ml, 42.3 mmol). The reaction mixture was stirred at −15° C. for 15 minutes, then reaction mixture was cooled down to −78° C. followed by addition of a solution of 4-chloro-3-cyclopropylpyridine (Example 48a, 1.3 g, 8.46 mmol) in dry toluene (9 ml). The resulting reaction mixture was stirred at −78° C. for 1 hour. Addition of carbon dioxide (3.72 g, 84.6 mmol) (pellets from a dry ice dispenser) into the mixture. The reaction mixture was let to warm up to −15° C. and kept at −15° C. for 1 hour. The reaction was quenched by addition of water and stirred at r.t for 15 min. The reaction mixture was diluted with ethyl acetate, poured into a separatory funnel and extracted with 4.0M aqueous solution hydrochloric acid (21.2 ml, 84.6 mmol). The organic phase was collected and the aqueous was back-extracted twice with ethylacetate. All organic phases were combined, dried over sodium sulfate and evaporated down to dryness to give a yellow oil. The former oil was dissolved in diethylether which gave a white suspension. The suspension was kept at 0° C. for few hours. The precipitate was collected by filtration, dried under high vacuum to yield the title compound (886 mg, 53%) as a white solid. MS (ESI, m/z): 196.0 (M−H+).

Provenance & Evidence