Toluene → 2-Pyridinemethanol, 5-(difluoromethoxy)-

HRID 15046

Reaction equation

HRID 15046 reaction equation
C1(C)C=CC=CC=1.[H-].C([Al+]CC(C)C)C(C)C.C([O:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:32])[F:31])=[CH:25][N:24]=1)=O)C.[BH4-].[Na+].O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>CO.C1COCC1>[F:32][CH:30]([F:31])[O:29][C:26]1[CH:27]=[CH:28][C:23]([CH2:21][OH:20])=[N:24][CH:25]=1

Participants

8

Reactant 5

HCID 1140TolueneHCID 62649Sodium sulfate decahydrateHCID 4311764Sodium borohydrideHCID 21225700DiisobutylaluminumhydrideHCID 68430338Ethyl 5-(difluoromethoxy)picolinate

Product 1

HCID 684317562-Pyridinemethanol, 5-(difluoromethoxy)-Yield 87%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A toluene solution (13.8 mL, 13.8 mmols) of 1N diisobutylaluminium hydride was added to a THF solution (40 mL) of 2-ethoxycarbonyl-5-difluoromethoxypyridine (1.0 g, 4.6 mols) and stirred at 0° C. for 40 minutes. Successively sodium borohydride (174 mg, 4.6 mmols) and methanol (2 mL) were added and stirred at 0° C. for 30 minutes. Sodium sulfate decahydrate was added to the reaction liquid and stirred overnight at room temperature. Filtering the insoluble matter with Celite, the solvent was concentrated under reduced pressure. The residue was purified on silica gel column chromatography (C-300, hexane:ethyl acetate=3:2-2:3) to provide the title compound (738 mg, 87%).

Workup

  1. stirringstirred at 0° C. for 30 minutes
  2. stirringstirred overnight at room temperature
  3. filtrationFiltering the insoluble matter with Celite
  4. concentrationthe solvent was concentrated under reduced pressure
  5. customThe residue was purified on silica gel column chromatography (C-300, hexane:ethyl acetate=3:2-2:3)

Sources & evidence

ORD record
ord-2b2063a5771f49eaa882928ed87a2712
Source dataset
uspto-grants-2010_06
Patent number
US07732456B2

Linked notes

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