Cesium carbonate → 2-Chloro-4-methyl-5-(2,2,2-trifluoroethoxyl)pyridine

HRID 715417Notes

Reaction equation

HRID 715417 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[C:4]([CH3:9])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[CH2:22][C:23]([F:26])([F:25])[F:24])(=O)=O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH3:9])[C:5]([O:8][CH2:22][C:23]([F:26])([F:25])[F:24])=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 712995492-Chloro-5-hydroxy-4-methylpyridine

Product 1

HCID 898739752-Chloro-4-methyl-5-(2,2,2-trifluoroethoxyl)pyridineYield 95.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 6-chloro-4-methylpyridin-3-ol (2.00 g, 13.9 mmol) and cesium carbonate (6.81 g, 20.9 mmol) in DMF (40 mL) is added dropwise 2,2,2-trifluoroethyl trifluoromethanesulfonate (3.56 g, 15.3 mmol) at 0° C. After stirring at rt for 1 hour, the mixture is poured onto water (300 mL). The aqueous layer is extracted with EtOAc (300 mL). The separated organic layer is washed with water (200 mL), dried over sodium sulfate, and concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (9:1) to give 3.00 g (95% yield) of the title compound as white solid.

Workup

  1. additionthe mixture is poured onto water (300 mL)
  2. extractionThe aqueous layer is extracted with EtOAc (300 mL)
  3. washThe separated organic layer is washed with water (200 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (9:1)

Sources & evidence

ORD record
ord-b55b27342eed4d93852f583a1fd4dd76
Source dataset
uspto-grants-2015_11
Patent number
US09187475B2

Reaction notes

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