2,2,2-Trifluoroethanol → 4-(4-Chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyrimidine-2-carboxylic acid methyl ester

HRID 1025955Notes

Reaction equation

HRID 1025955 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[C:8](F)=[CH:7][N:6]=1)=[O:4].C(=O)([O-])[O-].[Cs+].[Cs+].[F:25][C:26]([F:30])([F:29])[CH2:27][OH:28]>CS(C)=O>[CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[C:8]([O:28][CH2:27][C:26]([F:30])([F:29])[F:25])=[CH:7][N:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 10796Cesium carbonateHCID 66678591Methyl 4-(4-chlorophenyl)-5-fluoropyrimidine-2-carboxylate

Product 1

HCID 666870874-(4-Chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyrimidine-2-carboxylic acid methyl esterYield 86.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 0.143 g 4-(4-chloro-phenyl)-5-fluoro-pyrimidine-2-carboxylic acid methyl ester in 1.5 ml dried DMSO was added 192 mg of cesium carbonate and 0.059 g of 2,2,2-trifluoroethanol and the mixture was stirred at 60° C. for 2 hours. The reaction mixture was partitioned between water and ethyl acetate, the phases were separated and the organic phase was dried with MgSO4 and purified by chromatography on silica gel with a gradient of heptane:ethyl acetate=9:1 to 1:1 to yield 161 mg (86.60%) of the title compound as white solid, MS 347.1 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. customthe phases were separated
  3. dry with materialthe organic phase was dried with MgSO4
  4. custompurified by chromatography on silica gel with a gradient of heptane

Sources & evidence

ORD record
ord-85efa97045de493baecf7d59b685b8f4
Source dataset
uspto-grants-2014_05
Patent number
US08729105B2

Reaction notes

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