Acetaldehyde → 2,6-Difluoro-alpha-methyl-3-pyridinemethanol

HRID 1436101Notes

Reaction equation

HRID 1436101 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[N:15]=1.[CH:21](=[O:23])[CH3:22].Cl>CCCCCC.O1CCCC1.C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:13][C:14]1[C:19]([CH:21]([OH:23])[CH3:22])=[CH:18][CH:17]=[C:16]([F:20])[N:15]=1

Participants

10

Reactant 5

HCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 739342,6-DifluoropyridineHCID 178418339Butyllithium

Product 1

HCID 220383052,6-Difluoro-alpha-methyl-3-pyridinemethanol

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diisopropylamine (134 mL) was added dropwise to a mixed solution composed of a solution of n-butyl lithium in hexane (2.62 M, 368 mL) and tetrahydrofuran (800 mL) in a nitrogen atmosphere at −60° C. or less. The reaction solution was stirred for 30 minutes, and then a solution of 2,6-difluoropyridine (100 g) in tetrahydrofuran (100 mL) was added dropwise to the reaction solution at −60° C. or less. The reaction solution was stirred for one hour, and then acetaldehyde (97.6 mL) was added dropwise to the reaction solution. Then, 2 N aqueous hydrochloric acid (1,000 ml) was added dropwise to the reaction solution. Thereafter, ethyl acetate (1,000 mL) and toluene (1,000 mL) were added to the reaction solution, and the organic layer was separated. The organic layer was concentrated under reduced pressure to obtain 129 g of the title compound.

Workup

  1. stirringThe reaction solution was stirred for one hour
  2. customthe organic layer was separated
  3. concentrationThe organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-430eb45195ef4f4d8cd01392047a1a2b
Source dataset
uspto-grants-2009_11
Patent number
US07618960B2

Reaction notes

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