Reaction #78401

Reaction equation

magnesium sulfate

3-amino-2-chloropyridine

2,2,2-trifluoroethanol

trifluoroacetic acid

sodium bicarbonate

t-butyl nitrite

→

2-chloro-3-(2,2,2-trifluoroethoxy)pyridine

Conditions

Workup

1. 1
   Temperaturewhile maintaining the temperature in the range 15° C. to 20° C
2. 2
   Extractionextracted with MTBE
3. 3
   OtherThe solvent is removed by evaporation

Procedure

A reactor vessel is charged with 3-amino-2-chloropyridine (2.7 g, 21 mmol), 2,2,2-trifluoroethanol (15 g, 150 mmol), and trifluoroacetic acid (3.63 g, 31.8 mmol). The solution is cooled to 15° C. and magnesium sulfate (2.6 g) is charged to the vessel. The reagent t-butyl nitrite (2.51 g of a 96% solution, 23.4 mmol) is added drop-wise to the vessel while maintaining the temperature in the range 15° C. to 20° C. The solution is 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 (1.58 g, crude yield 35.6%).

Source