Bromomethyl 4-methoxyphenyl ketone → 2-(5-Benzyloxy-2-vinylphenoxy)-1-(4-methoxyphenyl)ethanone

HRID 254909Notes

Reaction equation

HRID 254909 reaction equation
[CH3:1]C(C)([O-])C.[K+].[CH2:7]([O:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=O)=[C:17]([OH:23])[CH:16]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Br[CH2:25][C:26]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=1)=[O:27]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH2:7]([O:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[CH2:1])=[C:17]([CH:16]=1)[O:23][CH2:25][C:26]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=1)=[O:27])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 4965Bromomethyl 4-methoxyphenyl ketoneHCID 5612354-Benzyloxy-2-hydroxybenzaldehydeHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 498213242-(5-Benzyloxy-2-vinylphenoxy)-1-(4-methoxyphenyl)ethanoneYield 80%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A suspension of methyl triphenyl phosphonium bromide (MTPPB, 16.90 g, 47.31 mmol) in anhydrous THF (50 mL) was cooled in an ice bath and added with potassium tert-butoxide (t-BuOK, 5.31 g, 47.32 mmol) in portions under nitrogen. After stirring at 0° C. for 15 min, a mixture of 4-benzyloxy-2-hydroxybenzaldehyde (1)(9.0 g, 39.43 mmol), t-BuOK (4.87 g, 43.40 mmol) and THF (50 mL) was added, and the resultant mixture was stirred at 0° C. for 2 hrs. Thereafter, the mixture was heated under reflux, and a solution of 2-bromo-4′-methoxyacetophenone (10.85 g, 47.36 mmol) in THF (30 mL) was added dropwise. After stirring under reflux for 1 hr (TLC monitoring), the mixture was quenched with a saturated NH4Cl solution. After removal of most of the THF in vacuo, the resultant residue was extracted six times with EtOAc (50 mL). The organic layers were combined, washed with a saturated NaCl solution, and dried with anhydrous MgSO4. After filtration, the filtrate was concentrated in vacua, followed by purification via silica gel column chromatography (ethyl acetate/n-hexane=1:15), thus giving the title compound 2a as a colorless crystal (11.81 g, 80% yield).

Workup

  1. temperaturewas cooled in an ice bath
  2. additionwas added
  3. temperatureThereafter, the mixture was heated
  4. temperatureunder reflux
  5. stirringAfter stirring
  6. temperatureunder reflux for 1 hr (TLC monitoring)
  7. customthe mixture was quenched with a saturated NH4Cl solution
  8. customAfter removal of most of the THF in vacuo
  9. extractionthe resultant residue was extracted six times with EtOAc (50 mL)
  10. washwashed with a saturated NaCl solution
  11. dry with materialdried with anhydrous MgSO4
  12. filtrationAfter filtration
  13. concentrationthe filtrate was concentrated in vacua
  14. customfollowed by purification via silica gel column chromatography (ethyl acetate/n-hexane=1:15)

Sources & evidence

ORD record
ord-93ce9ab0274c448492b6a600c3a032a3
Source dataset
uspto-grants-2011_01
Patent number
US07875736B2

Reaction notes

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