Water → 1-[(Benzyloxy)methyl]cyclopentanecarbonitrile

HRID 45048Notes

Reaction equation

HRID 45048 reaction equation
[OH:1][CH2:2][C:3]1([C:8]#[N:9])[CH2:7][CH2:6][CH2:5][CH2:4]1.[H-].[Na+].[CH2:12](Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.O>CN(C=O)C.[Cl-].[Na+].O>[CH2:12]([O:1][CH2:2][C:3]1([C:8]#[N:9])[CH2:7][CH2:6][CH2:5][CH2:4]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7498Benzyl Bromide2×HCID 24758Sodium hydride2×HCID 566871891-(Hydroxymethyl)cyclopentanecarbonitrile

Product 1

HCID 574780481-[(Benzyloxy)methyl]cyclopentanecarbonitrileYield 76.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 1-(hydroxymethyl)cyclopentanecarbonitrile (0.30 g, 2.0 mmol) in DMF (4 mL) was added sodium hydride (60% dispersion in mineral oil, 0.101 g, 2.52 mol). The resulting mixture was stirred for 20 minutes, followed by the addition of benzyl bromide (0.28 mL, 2.4 mmol). The reaction was stirred at ambient temperature for 64 hours. Additional sodium hydride (60% dispersion in mineral oil, 0.060 g, 1.5 mmol) and benzyl bromide (0.18 mL, 1.5 mmol) were added and the reaction was stirred for an additional 30 minutes. Water was then added to the mixture, followed by brine, and the aqueous layer was extracted with ethyl acetate. The extracts were combined and dried over sodium sulfate, and the solvent was then removed in vacuo. To the resulting residue was added water. The product was isolated by extraction with diethyl ether. The ethereal extracts were dried over sodium sulfate, and the solvent was evaporated. Flash column chromatography (eluting with a gradient from 0-30% ethyl acetate in hexanes) afforded product (330 mg, 64%).

Workup

  1. stirringThe reaction was stirred at ambient temperature for 64 hours
  2. stirringthe reaction was stirred for an additional 30 minutes
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. customthe solvent was then removed in vacuo
  6. additionTo the resulting residue was added water
  7. customThe product was isolated by extraction with diethyl ether
  8. dry with materialThe ethereal extracts were dried over sodium sulfate
  9. customthe solvent was evaporated
  10. washFlash column chromatography (eluting with a gradient from 0-30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-67a1dd0423644c8ca306374008c630f2
Source dataset
uspto-grants-2013_09
Patent number
US08541425B2

Reaction notes

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