Dimethylformamide → 5-Fluoro-2-[(1-methyl-1H-pyrazol-5-yl)methoxy]pyridine

HRID 238393Notes

Reaction equation

HRID 238393 reaction equation
[H-].[Na+].CN(C)C=O.[CH3:8][N:9]1[C:13]([CH2:14][OH:15])=[CH:12][CH:11]=[N:10]1.F[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1>O>[F:23][C:20]1[CH:21]=[CH:22][C:17]([O:15][CH2:14][C:13]2[N:9]([CH3:8])[N:10]=[CH:11][CH:12]=2)=[N:18][CH:19]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 27628712,5-DifluoropyridineHCID 11815316(1-methyl-1H-pyrazol-5-yl)methanol

Product 1

HCID 866848895-Fluoro-2-[(1-methyl-1H-pyrazol-5-yl)methoxy]pyridineYield 58.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

60% Sodium hydride (390 mg) was added to a dimethylformamide (9.0 mL) solution of (1-methyl-1H-pyrazol-5-yl)methanol (1.00 g) at a room temperature, and the obtained solution was then stirred for 2 hours. Thereafter, 2,5-difluoropyridine (1.17 g) was added to the reaction solution, and the mixed solution was then stirred for 16 hours. Subsequently, water was added to the reaction solution, and the obtained mixture was then extracted with hexane/ethyl acetate (1/2). The organic layer was concentrated under a reduced pressure. The residue was purified by column chromatography (silica gel cartridge, hexane/ethyl acetate=95:5 to 60:40), so as to obtain the title compound (1.08 g) in the form of a colorless solid.

Workup

  1. stirringthe mixed solution was then stirred for 16 hours
  2. extractionthe obtained mixture was then extracted with hexane/ethyl acetate (1/2)
  3. concentrationThe organic layer was concentrated under a reduced pressure
  4. customThe residue was purified by column chromatography (silica gel cartridge, hexane/ethyl acetate=95:5 to 60:40)

Sources & evidence

ORD record
ord-c45fde6b78664f38bfbe9e95d356dfa5
Source dataset
uspto-grants-2014_02
Patent number
US08642626B2

Reaction notes

Loading…