2-Methyl-5-hydroxypyridine → 2-Methyl-5-((1-methylcyclopropyl)methoxy)pyridine

HRID 511828Notes

Reaction equation

HRID 511828 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][C:10]1([CH2:13]O)[CH2:12][CH2:11]1.C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH2:9][C:10]2([CH3:13])[CH2:12][CH2:11]2)=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 142752-Methyl-5-hydroxypyridineHCID 137701(1-Methylcyclopropyl)methanolHCID 4622928Cyanomethylenetributylphosphorane

Product 1

HCID 672901652-Methyl-5-((1-methylcyclopropyl)methoxy)pyridineYield 100.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 6-methylpyridin-3-ol (0.5 g, 4.6 mmol) in toluene (6 mL) was added (1-methylcyclopropyl)methanol (0.59 g, 6.9 mmol) and stirred under nitrogen atmosphere. The solution was added cyanomethylenetri-n-butylphosphorane (CMBP, 2.5 ml, 9.53 mmol) and stirred at 100° C. for 3 hours. The reaction mixture was evaporated. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (2:1 (v/v)) to give 820 mg (quantitative yield) of the title compound as a brown oil:

Workup

  1. stirringstirred at 100° C. for 3 hours
  2. customThe reaction mixture was evaporated
  3. customThe residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (2:1 (v/v))

Sources & evidence

ORD record
ord-f6973ba081ce4450b2fbf930bedc4c6a
Source dataset
uspto-grants-2015_08
Patent number
US09101616B2

Reaction notes

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