Benzyl Bromide → Cyclohexanone, 4-[(phenylmethoxy)methyl]-

HRID 596114Notes

Reaction equation

HRID 596114 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([CH2:11][OH:12])[CH2:7][CH2:6]2)OCC1.[H-].[Na+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[OH-].[Na+]>CN(C=O)C>[CH2:15]([O:12][CH2:11][CH:8]1[CH2:7][CH2:6][C:5](=[O:1])[CH2:10][CH2:9]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 100808381,4-Dioxaspiro[4.5]decan-8-ylmethanol

Product 1

HCID 10443381Cyclohexanone, 4-[(phenylmethoxy)methyl]-Yield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1,4-dioxaspiro[4.5]decan-8-ylmethanol (1.33 g, 7.72 mmol) was dissolved in DMF (14 mL) and then cooled to 0° C. To the solution was added NaH (0.402 g, 10.04 mmol) in portions and the mixture agitated at 10° C. for 1 h and then benzyl bromide (1.194 mL, 10.04 mmol) was added and the mixture agitated over 72 h. The reaction mixture was quenched with water and extracted with ether and the combined organic extracts dried (MgSO4), filtered and concentrated in vacuo and the crude product 8-((benzyloxy)methyl)-1,4-dioxaspiro[4.5]decane dissolved in acetonitrile (35 mL) and water (25 mL) and treated with 3N HCl (13 mL) and agitated at room temperature for 20 min upon which LCMS indicated desired product. The reaction mixture was quenched with 40 mmol aqueous NaOH and then extracted with EtOAc (200 mL) and the organic layer was washed with water and dried (MgSO4), filtered and concentrated in vacuo and the residue purified by flash chromatography (0-50% EtOAc/heptane) to afford 1.23 g of the desired product as a colorless syrup (73%). LCMS (m/z): 329.2 (MH+), 1.33 min.

Workup

  1. stirringthe mixture agitated over 72 h
  2. customThe reaction mixture was quenched with water
  3. extractionextracted with ether
  4. dry with materialthe combined organic extracts dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionthe crude product 8-((benzyloxy)methyl)-1,4-dioxaspiro[4.5]decane dissolved in acetonitrile (35 mL)
  8. additionwater (25 mL) and treated with 3N HCl (13 mL)
  9. stirringagitated at room temperature for 20 min upon which LCMS
  10. extractionextracted with EtOAc (200 mL)
  11. washthe organic layer was washed with water
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customthe residue purified by flash chromatography (0-50% EtOAc/heptane)

Sources & evidence

ORD record
ord-e8968c09beeb4e35af9faaa79f0bc8be
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

Loading…