Reaction #78402

Reaction equation

2,2,2-trifluoroethanol

t-butyl nitrite

sodium bicarbonate

3-amino-2-chloropyridine

2,2,2-trifluoroethanol

trifluoroacetic acid

→

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

Yield 62.6%

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
   TemperatureAfter cooling the solution, it
4. 4
   Extractionextracted with MTBE
5. 5
   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 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 55° C. The temperature rose to 70° C. during the drop-wise addition of the diazonium salt reaction mass. After cooling the solution, it 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 (3.36 g) with an actual yield of 62.6%.

Source