Methanesulfonic Acid → 2-Chloro-3-(2,2,2-trifluoroethoxy)pyridine

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Reaction Steps

A reactor vessel is charged with 3-amino-2-chloropyridine (5.4 g, 42 mmol), 2,2,2-trifluoroethanol (50 g, 500 mmol), and methanesulfonic acid (4.1 g, 43 mmol). The solution is heated to the range 55° C. to 60° C. and then t-butyl nitrite (5.3 g of a 90% solution, 46 mmol) is added drop-wise to the vessel while maintaining the temperature at 60° C. to 65° C. After nitrogen evolution ceases, the solution is cooled, neutralized with aqueous saturated sodium bicarbonate solution and then extracted with MTBE. The solvent is removed by evaporation to obtain 2-chloro-3-(2,2,2-trifluoroethoxy)pyridine as a crude oil (11.1 g) with an actual yield of 67.3%.

Provenance & Evidence