Potassium Carbonate → 2-Bromo-5-(difluoromethoxy)pyridine

HRID 930339Notes

Reaction equation

HRID 930339 reaction equation
[Br:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Cl[C:10]([F:15])([F:14])C([O-])=O.[Na+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH:10]([F:15])[F:14])=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2734985Sodium chlorodifluoroacetateHCID 27628652-Bromo-5-hydroxypyridine

Product 1

HCID 231205792-Bromo-5-(difluoromethoxy)pyridineYield 55%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 6-bromopyridin-3-ol (1.20 g, 6.90 mmol), sodium 2-chloro-2,2-difluoroacetate (1.577 g, 10.35 mmol), and potassium carbonate (1.239 g, 8.97 mmol) in 10 mL of anhydrous DMF was heated at 85° C. for 1.5 days. The reaction mixture was diluted with 50 mL of EtOAc, washed with 50 mL of H2O, followed by washing with 50 mL of NaOH (1N) solution, the EtOAc layer was dried (Na2SO4) and concentrated to give a light brown oil that was purified by Shoko silica gel chromatography instrument eluting with 0-10% EtOAc in hexanes (0-10% over 25 min; GRACE column: 80 g pre-packed). Desired fraction were combined and concentrated to give the titled compound as a colorless oil: 0.85 g, 55% yield. MS m/z=223.9, 225.9 [M+H]+. Calculated for C6H4BrF2NO: 222.9, 224.9.

Workup

  1. washwashed with 50 mL of H2O
  2. washby washing with 50 mL of NaOH (1N) solution
  3. dry with materialthe EtOAc layer was dried (Na2SO4)
  4. concentrationconcentrated
  5. customto give a light brown oil that
  6. customwas purified by Shoko silica gel chromatography instrument
  7. washeluting with 0-10% EtOAc in hexanes (0-10% over 25 min; GRACE column: 80 g pre-packed)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3fc7d93122294b9a86ccfadeef8edda8
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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