Reaction #78407

Reaction equation

3-amino-2-bromopyridine

2,2,2-trifluoroethanol

methanesulfonic acid

sodium bicarbonate

t-butylnitrite

→

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

Conditions

Workup

1. 1
   TemperatureThe solution is heated to the range 65° C. to 70° C.
2. 2
   Temperaturewhile maintaining the temperature at 55° C. to 70° C
3. 3
   TemperatureAfter nitrogen evolution ceases, the solution is cooled
4. 4
   Extractionextracted with MTBE
5. 5
   OtherThe solvent is removed by evaporation

Procedure

A reactor vessel is charged with 3-amino-2-bromopyridine (2.0 g, 11.4 mmol), 2,2,2-trifluoroethanol (20 g, 200 mmol), and methanesulfonic acid (1.7 g, 18 mmol). The solution is heated to the range 65° C. to 70° C. and then t-butylnitrite (1.46 g of a 90% solution, 12.7 mmol) is added drop-wise to the vessel while maintaining the temperature at 55° C. to 70° 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-bromo-3-(2,2,2-trifluoroethoxy)pyridine as a crude oil (2.85 g, crude yield of 96%).

Source