Ethanol → Ethyl 5-(difluoromethoxy)picolinate

HRID 15045

Reaction equation

HRID 15045 reaction equation
CN([CH:4]=[O:5])C.[CH2:6]([OH:8])[CH3:7].Br[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH:17]([F:19])[F:18])=[CH:12][N:11]=1.C(N(CC)CC)C>[C]=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:6]([O:8][C:4]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH:17]([F:19])[F:18])=[CH:12][N:11]=1)=[O:5])[CH3:7]

Participants

8

Reactant 4

HCID 702EthanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 231205792-Bromo-5-(difluoromethoxy)pyridine

Product 1

HCID 68430338Ethyl 5-(difluoromethoxy)picolinateYield 80%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418416HCID 178418416, compoundSolvent

Procedure

A DMF (15 mL)-ethanol (15 mL) mixed solvent solution of 2-bromo-5-difluoromethoxypyridine (1.32 g, 5.89 mmols), palladium acetate (132 mg, 0.59 mmol), 1,1′-bis(diphenylphosphino)ferrocene (654 mg, 1.18 mmols) and triethylamine (1.6 mL, 11.8 mmols) was stirred overnight at 50° C. in carbon monoxide atmosphere. The reaction liquid was cooled to room temperature and the solvent was concentrated under reduced pressure. Ethyl acetate was added to the resulting residue, followed by washing with water and drying over anhydrous magnesium sulfate. Concentrating the solvent under reduced pressure, the residue was purified on silica gel column chromatography (C-300, hexane:ethyl acetate=4:1-3:2) to provide the title compound (1.03 g, 80%).

Workup

  1. customThe reaction liquid
  2. concentrationthe solvent was concentrated under reduced pressure
  3. additionEthyl acetate was added to the resulting residue
  4. washby washing with water
  5. dry with materialdrying over anhydrous magnesium sulfate
  6. concentrationConcentrating the solvent under reduced pressure
  7. customthe residue was purified on silica gel column chromatography (C-300, hexane:ethyl acetate=4:1-3:2)

Sources & evidence

ORD record
ord-c61847675b0b4ea78310640084b42d11
Source dataset
uspto-grants-2010_06
Patent number
US07732456B2

Linked notes

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