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

HRID 517046Notes

Reaction equation

HRID 517046 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+].[F:14][C:15]([F:26])([F:25])[CH2:16]OS(C(F)(F)F)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:16][C:15]([F:26])([F:25])[F:14])=[CH:7][N:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 24758Sodium hydrideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonate2×HCID 4715126Methyl 5-hydroxypyridine-2-carboxylate

Product 1

HCID 57475873Methyl 5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Under an atmosphere of nitrogen a solution of 5-hydroxy-pyridine-2-carboxylic acid methyl ester (200 mg, 1.31 mmol) in N,N-dimethylformamide (2 ml) was treated at room temperature with sodium hydride (55% dispersion in oil, 64 mg). After the gas formation had ceased, the suspension was cooled to 0° C. and trifluoro-methanesulphonic acid 2,2,2-trifluoro-ethyl ester (364 mg, 1.57 mmol) was added. After stirring at room temperature for 2 hours about 50% of the starting material was left. Another 364 mg of trifluoro-methanesulphonic acid 2,2,2-trifluoro-ethyl ester were added and after 30 minutes the reaction was complete. For the workup, the reaction mixture was treated with a saturated solution of sodium carbonate, then extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over sodium sulphate, and evaporated at reduced pressure. The crude product was purified by chromatography on silica gel using a 3:1-mixture of heptane and ethyl acetate as the eluent. The 5-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid methyl ester was obtained as a white solid (216 mg, 70% of theory). MS (ISP): m/z=236.3 [M+H]+.

Workup

  1. waitwas left
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulphate
  5. customevaporated at reduced pressure
  6. customThe crude product was purified by chromatography on silica gel using a 3

Sources & evidence

ORD record
ord-d40aa0745986460ba53cc5bc078d940d
Source dataset
uspto-grants-2015_08
Patent number
US09115098B2

Reaction notes

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