4'-Hydroxyacetophenone → 1-[4-(Benzyloxy)phenyl]ethan-1-one

HRID 1093627Notes

Reaction equation

HRID 1093627 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C=O)C>[CH2:17]([O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 74694'-HydroxyacetophenoneHCID 7498Benzyl BromideHCID 11430Potassium Carbonate

Product 1

HCID 2452261-[4-(Benzyloxy)phenyl]ethan-1-oneYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-hydroxy-phenyl)-ethanone (10 g, 0.0735 mole) in DMF (50 mL) was added K2CO3 (20.2 g, 0.147 mole) at ambient temperature. Benzyl bromide (13.83 g, 0.0808 mole) was then added and the resulting mixture was stirred at ambient temperature for 5 hours. The reaction mixture was then quenched with iced water. The resulting precipitate was isolated by filtration and dried to afford 16.2 g (98%) of 1-(4-benzyloxy-phenyl)-ethanone. LCMS: 227.1 (M+1)+, 98.38%. A mixture of THF (130 mL) and NaH (60% w/w dispersion in oil) (5.28 g, 0.132 mole) was cooled to 0° C. with stirring for 5 minutes. Diethyl oxalate (12.87 g, 0.0886 mole) was added and the mixture was heated to reflux for 15 minutes. after cooling to ambient temperature 1-(4-benzyloxy-phenyl)-ethanone (10 g, 0.0442 mole) in THF (50 mL) was added dropwise over a period of 45 minutes. The resulting mixture was heated to 70° C. for 1 hour. The reaction mixture was then quenched with cold aqueous NH4Cl solution. The resulting precipitate was isolated by filtration and dried to afford 21.2 g of 4-(4-benzyloxy-phenyl)-2,4-dioxo-butyric acid ethyl ester. LCMS: 327.12 (M+1)+, 36.5%. A solution of 4-(4-benzyloxy-phenyl)-2,4-dioxo-butyric acid ethyl ester (10 g, 0.03064 mole), acetic acid (20 mL) and hydrazine hydrate (1.685 g, 0.0337 mole) was heated to reflux for 8 hours. The reaction mixture was then poured into iced water and basified with saturated aqueous NaHCO3 solution. The product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to afford 6.3 g (64%) of 5-(4-benzyloxy-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester. LCMS: 323.13 (M+1)+, 95.10%.

Workup

  1. customThe reaction mixture was then quenched with iced water
  2. customThe resulting precipitate was isolated by filtration
  3. customdried

Sources & evidence

ORD record
ord-eb94442c14024979b9a49d63b432f33a
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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