Potassium Hydroxide → 1-(3,4-Difluorophenyl)-2-hydroxy-propan-1-one dimethyl acetal

HRID 1167712Notes

Reaction equation

HRID 1167712 reaction equation
[OH-].[K+].[F:3][C:4]1[CH:5]=[C:6]([C:11](=[O:15])[CH:12]([OH:14])[CH3:13])[CH:7]=[CH:8][C:9]=1[F:10].[C:16](O)(=[O:18])C.[C:20](O)(=O)C.IC1C=CC=CC=1>CO>[CH3:20][O:15][C:11]([O:18][CH3:16])([C:6]1[CH:7]=[CH:8][C:9]([F:10])=[C:4]([F:3])[CH:5]=1)[CH:12]([OH:14])[CH3:13]

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 12217721Iodo benzene diacetateHCID 229935141-(3,4-Difluorophenyl)-2-hydroxy-propan-1-one

Product 1

HCID 229934911-(3,4-Difluorophenyl)-2-hydroxy-propan-1-one dimethyl acetal

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
0 °C

Procedure

In a round bottom flask containing 200 mL of MeOH was added pellets of potassium hydroxide (23.0 g, 410.0 mmol). The solution was cooled to 0° C. and 1-(3,4-difluorophenyl)-2-hydroxy-propan-1-one (7.0 g, 41.2 mmol) in 10 mL MeOH was added dropwise. The solution was stirred for 10 min and then iodobenzene diacetate (22.5 g, 70 mmol) was added in two portions. The solution first became orange and then turned yellow. It was stirred overnight at room temperature and then solvent was removed in vacuo. The residue was dissolved in water and was extracted with ethyl acetate (3×100 mL). The combined organic extracts were washed with brine and then dried over Na2SO4. After filteration, the solvent was removed in vacuo to get 1-(3,4-difluorophenyl)-2-hydroxy-propan-1-one dimethyl acetal as a yellow viscous oil (crude wt.=9.2 g). It was dissolved in 150 mL of acetone and 10 drops of concentrated sulfuric acid were added. After stirring for 3 h, TLC analysis indicated that the reaction was complete. Acetone was removed in vacuo and after basification with saturated NaHCO3, the residue was extracted in EtOAc and was washed with brine. The organic layer was separated, dried over Na2SO4 and then filtered. The solvent was removed in vacuo and the residue was purified by silica gel chromatography (Rf=0.4, 3:2 hexane/EtOAc) to obtain 1-(3,4-difluorophenyl)-2-hydroxy-propan-1-one as a pale yellow oil (3.3 g, 51% yield over two steps).

Workup

  1. stirringIt was stirred overnight at room temperature
  2. customsolvent was removed in vacuo
  3. dissolutionThe residue was dissolved in water
  4. extractionwas extracted with ethyl acetate (3×100 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. customAfter filteration, the solvent was removed in vacuo

Sources & evidence

ORD record
ord-26b5630a75724f468239dffb156412f3
Source dataset
uspto-grants-2003_09
Patent number
US06620815B1

Reaction notes

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