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

HRID 50129Notes

Reaction equation

HRID 50129 reaction equation
N[C:2]1[C:3]([Br:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[F:9][C:10]([F:14])([F:13])[CH2:11][OH:12].CS(O)(=O)=O.C(ON=O)(C)(C)C.C(=O)(O)[O-].[Na+]>>[Br:8][C:3]1[C:2]([O:12][CH2:11][C:10]([F:14])([F:13])[F:9])=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 5

HCID 6395Methanesulfonic AcidHCID 64092,2,2-TrifluoroethanolHCID 10906Tert-Butyl nitriteHCID 516892Sodium BicarbonateHCID 6428163-Amino-2-bromopyridine

Product 1

HCID 120567292-Bromo-3-(2,2,2-trifluoroethoxy)pyridine

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%).

Workup

  1. temperatureThe solution is heated to the range 65° C. to 70° C.
  2. temperaturewhile maintaining the temperature at 55° C. to 70° C
  3. temperatureAfter nitrogen evolution ceases, the solution is cooled
  4. extractionextracted with MTBE
  5. customThe solvent is removed by evaporation

Sources & evidence

ORD record
ord-9c059d5696554ab289e61c04dd4512ad
Source dataset
uspto-grants-2004_03
Patent number
US06710180B2

Reaction notes

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