Cyclopropanemethanol → 2-(4-Chloro-phenyl)-3-cyclopropylmethoxy-pyridine

HRID 1528371Notes

Reaction equation

HRID 1528371 reaction equation
[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[C:18](F)=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1>CS(C)=O>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[C:18]([O:5][CH2:4][CH:1]3[CH2:3][CH2:2]3)=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:11][CH:12]=1

Participants

4

Reactant 2

HCID 75644CyclopropanemethanolHCID 666786032-(4-Chloro-phenyl)-3-fluoro-pyridine

Product 1

HCID 666786972-(4-Chloro-phenyl)-3-cyclopropylmethoxy-pyridineYield 74.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a mixture of 16.20 g cyclopropanmethanol in 150 ml dry DMSO 11 g sodium hydride (55%) was added and the mixture was stirred at room temperature for 30 minutes. A solution containing 37.30 g 2-(4-chloro-phenyl)-3-fluoro-pyridine in 50 mL dry DMSO was added dropwise. The reaction mixture was then stirred at room temperature for 3 h. The resulting suspension was partitioned between water and methylene chloride, the phases were separated. The organic phase was washed with brine; then dried over MgSO4 and purified by chromatography on silica gel with a gradient of heptane to heptane:ethylacetate=2:1 to yield 34.95 g (74.90%) of the title compound as yellow oil, MS 260.1 (M+H)+.

Workup

  1. additionwas added
  2. additionwas added dropwise
  3. stirringThe reaction mixture was then stirred at room temperature for 3 h
  4. customThe resulting suspension was partitioned between water and methylene chloride
  5. customthe phases were separated
  6. washThe organic phase was washed with brine
  7. dry with materialthen dried over MgSO4
  8. custompurified by chromatography on silica gel with a gradient of heptane to heptane

Sources & evidence

ORD record
ord-4ee7da4803f24d1f8a5b3a33b439ba00
Source dataset
uspto-grants-2015_07
Patent number
US09090599B2

Reaction notes

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