Sodium hydride → 4-(5,7-Dioxaspiro[2.5]oct-6-ylmethoxy)-2,3-dimethylpyridine 1-oxide

HRID 1645509Notes

Reaction equation

HRID 1645509 reaction equation
[CH2:1]1[C:3]2([CH2:8][O:7][CH:6]([CH2:9][OH:10])[O:5][CH2:4]2)[CH2:2]1.[H-].[Na+].Cl[C:14]1[CH:19]=[CH:18][N+:17]([O-:20])=[C:16]([CH3:21])[C:15]=1[CH3:22]>CS(C)=O>[CH2:2]1[C:3]2([CH2:8][O:7][CH:6]([CH2:9][O:10][C:14]3[CH:19]=[CH:18][N+:17]([O-:20])=[C:16]([CH3:21])[C:15]=3[CH3:22])[O:5][CH2:4]2)[CH2:1]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 98774464-Chloro-2,3-dimethyl-1-oxidopyridin-1-iumHCID 597925305,7-Dioxaspiro[2.5]oct-6-ylmethanol

Product 1

HCID 597925884-(5,7-Dioxaspiro[2.5]oct-6-ylmethoxy)-2,3-dimethylpyridine 1-oxideYield 57.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

The 5,7-dioxaspiro[2.5]oct-6-ylmethanol (1.7 g, 11.8 mmol) obtained by the step (2b) was mixed with sodium hydride, in oil (708 mg, 17.7 mmol as the content was regarded as 60%) and dimethylsulfoxide (20 ml), and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture, 4-chloro-2,3-dimethylpyridine 1-oxide (1.86 g, 11.8 mmol) was added and stirred at 50° C. overnight. After dimethylsulfoxide was distilled off, methanol and NH silica gel were added to the residue and methanol was distilled off. The mixture of the reaction mixture and NH silica gel was purified by silica gel column chromatography (NH silica gel: 200 g, elution solvent: ethyl acetate/heptane=1/1 to 4/1→methanol/ethyl acetate=1/9 to 1/4) to obtain the title compound (1.8 g, yield: 57.5%) as a red oil.

Workup

  1. stirringstirred at 50° C. overnight
  2. distillationAfter dimethylsulfoxide was distilled off
  3. additionmethanol and NH silica gel were added to the residue and methanol
  4. distillationwas distilled off
  5. additionThe mixture of the reaction mixture and NH silica gel
  6. customwas purified by silica gel column chromatography (NH silica gel: 200 g, elution solvent: ethyl acetate/heptane=1/1 to 4/1→methanol/ethyl acetate=1/9 to 1/4)

Sources & evidence

ORD record
ord-e0679259513c43a9bdced7d8e745cc16
Source dataset
uspto-grants-2012_02
Patent number
US08124780B2

Reaction notes

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