Sodium hydride → Methyl 5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylate

HRID 1186192Notes

Reaction equation

HRID 1186192 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][N:6]=1)=[O:4].[H-].[Na+].FC(F)(F)S(O[CH2:20][C:21]([F:24])([F:23])[F:22])(=O)=O>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:20][C:21]([F:24])([F:23])[F:22])=[CH:7][N:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 4715126Methyl 5-hydroxypyridine-2-carboxylate

Product 1

HCID 57475873Methyl 5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylateYield 70.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-hydroxy-pyridine-2-carboxylic acid methyl ester (200 mg) in DMF (2.0 ml) was added at 22° C. NaH (55% in oil, 64 mg) and stirring was continued until gas evolution ceased. The suspension was cooled to 0° C. and treated with trifluoroethyl trifluormethane sulphonate (728 mg) and stirring was continued at 22° C. for 2 h. The mixture was partitioned between saturated NaHCO3 and ethyl acetate and the organic layer was dried and evaporated. The residue was purified by chromatography on silica using n-heptane/ethyl acetate (3:1) to give 5-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid methyl ester (216 mg) as a white solid. MS (ISP): m/z=236.3 [M+H]+.

Workup

  1. customThe mixture was partitioned between saturated NaHCO3 and ethyl acetate
  2. customthe organic layer was dried
  3. customevaporated
  4. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-ab9277e42f1c4422a7183475775bdfce
Source dataset
uspto-grants-2014_03
Patent number
US08673894B2

Reaction notes

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