Chloromethyl Methyl Ether → 5-(Methoxymethoxy)pyridine-2-carbonitrile

HRID 589932Notes

Reaction equation

HRID 589932 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]#[N:11])=[N:8][CH:9]=1.[CH3:12][O:13][CH2:14]Cl.[Cl-].[NH4+]>C(OCC)(=O)C.O.CN(C)C=O>[CH3:12][O:13][CH2:14][O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]#[N:11])=[N:8][CH:9]=1

Participants

8

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 214137735-Hydroxypyridine-2-carbonitrile

Product 1

HCID 574336675-(Methoxymethoxy)pyridine-2-carbonitrileYield 87.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

60% sodium hydride (3.62 g, 90.4 mmol) was added to an N,N-dimethylformamide (70 mL) solution of 5-hydroxypyridin-2-carbonitrile (7.24 g, 60.3 mmol) at 0° C., and the mixture was stirred at the same temperature for 15 minutes. Subsequently, chloromethyl methyl ether (9.16 ml, 121 mmol) was added to the mixture little by little, and the resulting mixture was further stirred at the same temperature for 45 minutes. A saturated aqueous solution of ammonium chloride and water were added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layer thus obtained was washed with brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=75:25, v/v) to give the title compound (8.63 g, yield: 87%).

Workup

  1. stirringwas further stirred at the same temperature for 45 minutes
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. customThe organic layer thus obtained
  4. washwas washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe resulting residue was purified by silica gel column chromatography (hexane

Sources & evidence

ORD record
ord-4e8c5a288c8d440aa2139c1c067b9fc0
Source dataset
uspto-grants-2016_01
Patent number
US09233958B2

Reaction notes

Loading…