Chlorodifluoromethane → 6-Bromo-3-difluoromethoxy-2,4-dimethyl-pyridine

HRID 1662214Notes

Reaction equation

HRID 1662214 reaction equation
CC(C)=O.C(=O)=O.[Br:8][C:9]1[N:14]=[C:13]([CH3:15])[C:12]([OH:16])=[C:11]([CH3:17])[CH:10]=1.Cl[CH:19]([F:21])[F:20]>C(O)(C)C.[OH-].[Na+]>[Br:8][C:9]1[N:14]=[C:13]([CH3:15])[C:12]([O:16][CH:19]([F:21])[F:20])=[C:11]([CH3:17])[CH:10]=1

Participants

6

Reactant 3

HCID 6372ChlorodifluoromethaneHCID 18522661Acetone cardiceHCID 593274926-Bromo-2,4-dimethylpyridin-3-ol

Product 1

HCID 585795136-Bromo-3-difluoromethoxy-2,4-dimethyl-pyridineYield 60%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

A three-necked round bottom flask (500 mL) equipped with dry ice condenser (−78° C., acetone/dry ice) was charged with a solution of 6-bromo-2,4-dimethyl-3-hydroxypyridine (7.2 g, 35.6 mmol) in i-propanol (100 mL) and aqueous sodium hydroxide solution (20%, 100 mL) was added. The reaction mixture was stirred vigorously at 40° C. for 5 hours while chlorodifluoromethane was bubbled continuously into the solution at a moderate rate. The reaction mixture was then cooled to room temperature and extracted with Et2O (3×100 mL). The combined extracts were washed with water (2×50 mL), dried over magnesium sulfate and concentrated in vacuo. Purification of the crude mixture by flash column chromatography using 5% ethyl acetate in hexane afforded the title compound (5.4 g, 60%).

Workup

  1. additionwas added
  2. customwas bubbled continuously into the solution at a moderate rate
  3. extractionextracted with Et2O (3×100 mL)
  4. washThe combined extracts were washed with water (2×50 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the crude mixture by flash column chromatography

Sources & evidence

ORD record
ord-da55c1a35da5496c821cd80c3c311778
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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