Reaction #78403

Reaction equation

t-butyl nitrite

2,2,2-trifluoroethanol

3-amino-2-chloropyridine

2,2,2-trifluoroethanol

methanesulfonic acid

magnesium sulfate

sodium bicarbonate

→

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

Yield 70.1%

Conditions

Workup

1. 1
   TemperatureThe solution is cooled to the range 0° C. to 5° C.
2. 2
   Temperaturemaintaining the temperature in the range 0° C. to 5° C
3. 3
   Temperaturemaintained at 65° C. to 70° C
4. 4
   TemperatureAfter cooling the solution it
5. 5
   Extractionextracted with MTBE
6. 6
   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), methanesulfonic acid (2.02 g, 21 mmol), and magnesium sulfate (3 g). The solution is cooled to the range 0° C. to 5° C. and then the reagent t-butyl nitrite (2.51 g of a 96% solution, 23.4 mmol) is added drop-wise to the vessel maintaining the temperature in the range 0° C. to 5° C. After stirring a few minutes the solution is transferred drop-wise to a reactor vessel containing 2,2,2-trifluoroethanol (20 g, 200 mmol) maintained at 65° C. to 70° C. After cooling the solution it 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 (4.4 g) with an actual yield of 70.1%.

Source