Water → 3-Bromo-6-(2,2-difluoroethoxy)-2-methylpyridine

HRID 623537Notes

Reaction equation

HRID 623537 reaction equation
[Br:1][C:2]1[C:3]([CH3:9])=[N:4][C:5](Br)=[CH:6][CH:7]=1.[F:10][CH:11]([F:14])[CH2:12][OH:13].CC(C)([O-])C.[K+].O>C1COCC1>[Br:1][C:2]1[C:3]([CH3:9])=[N:4][C:5]([O:13][CH2:12][CH:11]([F:14])[F:10])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1361872,2-Difluoroethan-1-olHCID 27629463,6-Dibromo-2-methylpyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 874266193-Bromo-6-(2,2-difluoroethoxy)-2-methylpyridineYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 3,6-dibromo-2-methylpyridine (2.00 g, 7.97 mmol) and 2,2-difluoroethanol (981 mg, 12.0 mmol) in THF (100 mL) is added potassium tert-butoxide (1.34 g, 12.0 mmol), and the mixture is stirred at 70° C. for 12 hours. After cooling to room temperature, the resulting mixture is poured to water (200 mL). The aqueous layer is extracted with ethyl acetate (200 mL×2). The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-hexane/ethyl acetate (8:1) to give 1.94 g (97% yield) of the title compound as colorless oil.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous layer is extracted with ethyl acetate (200 mL×2)
  3. dry with materialThe organic layer is dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/ethyl acetate (8:1)

Sources & evidence

ORD record
ord-372c676eed334e82bd7d0306c2966254
Source dataset
uspto-grants-2016_04
Patent number
US09302991B2

Reaction notes

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