Hydrochloric Acid → 6-(2,2,2-Trifluoroethoxy)pyridine-3-carboxylic acid

HRID 623419Notes

Reaction equation

HRID 623419 reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[F:11][C:12]([F:16])([F:15])[CH2:13][OH:14].[H-].[Na+].Cl>CN(C)C(=O)C>[F:11][C:12]([F:16])([F:15])[CH2:13][O:14][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 792226-Chloronicotinic acid

Product 1

HCID 27810286-(2,2,2-Trifluoroethoxy)pyridine-3-carboxylic acidYield 78%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-chloronicotinic acid (7.0 g, 44.4 mmol), 2,2,2-trifluoroethanol (6.40 mL, 89.0 mmol) and sodium hydride (5.33 g, 133.0 mmol, 60% in oil) in N,N-dimethylacetamide (400 mL) is stirred at 90° C. for 21 hours. After cooling to room temperature, the reaction mixture is poured slowly into 2M hydrochloric acid (300 mL) and extracted with n-hexane/ethyl acetate (1:10, 500 mL). The organic layer is washed with 2M hydrochloric acid (300 mL×2) and dried over sodium sulfate. The organic solvent is concentrated under reduced pressure to give 7.64 g (78% yield) of the title compound as colorless oil. This material is used for the next reaction (Step-2) without further purification.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with n-hexane/ethyl acetate (1:10, 500 mL)
  3. washThe organic layer is washed with 2M hydrochloric acid (300 mL×2)
  4. dry with materialdried over sodium sulfate
  5. concentrationThe organic solvent is concentrated under reduced pressure

Sources & evidence

ORD record
ord-fbf5850f891b43c3ae2c0bee52b1f62b
Source dataset
uspto-grants-2016_04
Patent number
US09302991B2

Reaction notes

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