Water → Methyl 5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylate

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Reaction Steps

To a solution of methyl 5-chloropyrazine-2-carboxylate (25 g, 144.87 mmol) in DMF (250 mL) under nitrogen atmosphere is added cesium carbonate (47.2 g, 144.8 mmol) and 2,2,2-trifluoro-ethanol (15.7 mL, 217.3 mmol). The reaction mixture is stirred 72 hours at room temperature. The mixture is poured over water (1 L) and a pale brown solid is collected by filtration. The solid is washed with water and dried under vacuum to a constant weight. The dry crude material is recrystallized twice from a mixture of water (200 mL) and isopropyl alcohol (40 ml) to yield the intermediate methyl 5-(2,2,2-trifluoroethoxyl)pyridine-2-carboxylate (15 g, 93%) as a pale cream solid and is used without further purification. A solution of intermediate methyl 5-(2,2,2-trifluoroethoxyl)pyridine-2-carboxylate (5 g, 21.17 mmol) in methanol (50 mL) and 1 M sodium hydroxide aqueous solution (42.3 mL, 42.3 mmol) is stirred at room temperature for 2 hours. Hydrochloric acid 35% w/w is added to adjust the ph to 2. Methanol is evaporated and a pale cream solid is isolated by filtration. The solid is washed with water and dried under vacuum to give the title compound (3 g, 51%). ES/MS (m/z): 223.1 (M+1).

Provenance & Evidence