Carbon Dioxide → 5-Cyclopropyl-4-cyclopropylmethoxy-pyridine-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of N,N-Dimethylethanolamine (CAN 108-01-0, 2.372 g, 3.08 mL, 30.6 mmol) in hexane cooled at −15° C. under an argon atmosphere was slowly added BuLi 1.6M in Hexane (38.2 mL, 61.1 mmol). The reaction was stirred at −15° C. during 20 minutes and was then cooled down to −78° C. before addition of 3-cyclopropyl-4-cyclopropylmethoxypyridine (Example 42b, 2.314 g, 12.2 mmol). The reaction was stirred 1 hour at −78° C. followed by addition of carbon dioxide (2.09 g, 47.6 mmol) (pellets from a dry ice dispenser) into the mixture. A white precipitate formed and the reaction was slowly warmed up to −20° C. The reaction was quenched with water, stirred 5 minutes and the volatiles were removed in vacuo. The residue was suspended into ethylacetate and extracted with 19 mL of a 2.0M aqueous solution hydrochloric acid. The organic phase was collected, dried over sodium sulfate and evaporated down to dryness to give an yellow oil. The former oil was dissolved in diethylether which gave a white precipitate. The suspension was stored at 0° C. for 1 hour and the solution was separated from the white solid. The white solid was dried under high vacuum to give the titled compound (815 mg, 66%). MS (ESI, m/z): 234.2 (M+H+).

Provenance & Evidence