Hydrochloric Acid → 6-(2,2,2-Trifluoroethoxy)pyridine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloronicotinic acid (7.0 g, 44.4 mmol), 2,2,2-trifluoroethanol (6.40 mL, 89.0 mmol) and sodium hydride (5.33 g, 133.0 mmol, 60% in oil) in N,N-dimethylacetamide (400 mL) is stirred at 90° C. for 21 hours. After cooling to room temperature, the reaction mixture is poured slowly into 2M hydrochloric acid (300 mL) and extracted with n-hexane/ethyl acetate (1:10, 500 mL). The organic layer is washed with 2M hydrochloric acid (300 mL×2) and dried over sodium sulfate. The organic solvent is concentrated under reduced pressure to give 7.64 g (78% yield) of the title compound as colorless oil. This material is used for the next reaction (Step-2) without further purification.

Provenance & Evidence