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

HRID 707382Notes

Reaction equation

HRID 707382 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][N:3]=1.Cl[C:10]([F:15])([F:14])C([O-])=O.[Na+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:10]([F:15])[F:14])=[CH:4][N:3]=1

Participants

5

Reactant 3

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

Product 1

HCID 231205792-Bromo-5-(difluoromethoxy)pyridineYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-bromo-5-hydroxypyridine (1.2 g, 6.9 mmol), sodium chlorodifluoroacetate (2.1 g, 13.8 mmol), and potassium carbonate (1.24 g, 8.97 mmol) in anhydrous DMF (10 ml) was stirred at 80° C. for 20 h. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The aqueous layer was back extracted with EtOAc and the combined organics was dried (Na2SO4) and concentrated. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 10% EtOAc in hexane, to provide 2-bromo-5-(difluoromethoxy)pyridine (0.89 g, 4.0 mmol, 58% yield) as colorless oil. ESI (M+1) 225.8.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture was partitioned between EtOAc and water
  3. extractionThe aqueous layer was back extracted with EtOAc
  4. dry with materialthe combined organics was dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  7. washeluting with a gradient of 0% to 10% EtOAc in hexane

Sources & evidence

ORD record
ord-f3e9e280b5d444e49a410fdb178d47d6
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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