2,2,2-Trifluoroethanol → 3-(2,2,2-Trifluoroethoxy)pyridine-2-carboxylic acid

HRID 341564Notes

Reaction equation

HRID 341564 reaction equation
CC(C)([O-])C.[K+].[F:7][C:8]([F:12])([F:11])[CH2:9][OH:10].F[C:14]1[C:15]([C:20]([OH:22])=[O:21])=[N:16][CH:17]=[CH:18][CH:19]=1>O>[F:7][C:8]([F:12])([F:11])[CH2:9][O:10][C:14]1[C:15]([C:20]([OH:22])=[O:21])=[N:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 27627863-Fluoropyridine-2-carboxylic acidHCID 23665647Potassium tert-butoxide

Product 1

HCID 574758793-(2,2,2-Trifluoroethoxy)pyridine-2-carboxylic acidYield 49%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Potassium tert-butoxide (954 mg, 8.51 mmol) was charged to a sealed tube with 2,2,2-trifluoroethanol (4 mL) and 3-fluoropyridine-2-carboxylic acid (400 mg, 2.84 mmol) and the mixture was heated to 130 C for 26 h, then to 150 C for 4 h, and then to 120 C for approximately 18 h. The mixture was diluted with water (6 mL) and washed with DCM (2×4 mL), which was then discarded. 1M HCl was added to bring the solution to pH 7 and the aqueous was extracted with DCM (2×4 mL). The extraction process was repeated as above at pH 5, 4 and 3. The combined organic extractions were dried over sodium sulfate and evaporated under vacuum to afford the title compound as a white solid (305 mg, 49%). Method B HPLC-MS: MH+ requires m/z=222. Found: m/z=222, Rt=0.73 min (100%).

Workup

  1. temperaturethe mixture was heated to 130 C for 26 h
  2. waitto 120 C for approximately 18 h
  3. washwashed with DCM (2×4 mL), which
  4. addition1M HCl was added
  5. extractionthe aqueous was extracted with DCM (2×4 mL)
  6. extractionThe combined organic extractions
  7. dry with materialwere dried over sodium sulfate
  8. customevaporated under vacuum

Sources & evidence

ORD record
ord-2d9fe477dafa4577916b6fc50060584f
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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