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

HRID 50127

Reaction equation

HRID 50127 reaction equation
N[C:2]1[C:3]([Cl: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.N(OC(C)(C)C)=O.C(=O)(O)[O-].[Na+]>>[Cl: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 805282-Chloro-3-pyridylamineHCID 516892Sodium Bicarbonate

Product 1

HCID 120567282-Chloro-3-(2,2,2-trifluoroethoxy)pyridineYield 67.3%

Procedure

A reactor vessel is charged with 3-amino-2-chloropyridine (5.4 g, 42 mmol), 2,2,2-trifluoroethanol (50 g, 500 mmol), and methanesulfonic acid (4.1 g, 43 mmol). The solution is heated to the range 55° C. to 60° C. and then t-butyl nitrite (5.3 g of a 90% solution, 46 mmol) is added drop-wise to the vessel while maintaining the temperature at 60° C. to 65° 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-chloro-3-(2,2,2-trifluoroethoxy)pyridine as a crude oil (11.1 g) with an actual yield of 67.3%.

Workup

  1. temperatureThe solution is heated to the range 55° C. to 60° C.
  2. temperaturewhile maintaining the temperature at 60° C. to 65° 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-178acea5fc59416fa07e80f9c264941c
Source dataset
uspto-grants-2004_03
Patent number
US06710180B2

Linked notes

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