Hydrochloric Acid → 1-(3,4-Difluoro-2-hydroxyphenyl)propan-1-one

HRID 1362499Notes

Reaction equation

HRID 1362499 reaction equation
C([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:7]=1[F:13])(=O)CC.[Cl-].[Cl-].[Cl-].[Al+3].Cl>ClC1C=CC=CC=1Cl.ClCCl>[F:13][C:7]1[C:6]([OH:5])=[C:11]([C:6](=[O:5])[CH2:7][CH3:8])[CH:10]=[CH:9][C:8]=1[F:12]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6451240Aluminum(III) ChlorideHCID 669694902,3-Difluorophenyl propionate

Product 1

HCID 216615951-(3,4-Difluoro-2-hydroxyphenyl)propan-1-oneYield 143.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 72391,2-DichlorobenzeneSolvent2×

Conditions

Temperature
100 °C

Procedure

30.1 g (161 mmol) of 2,3-difluorophenyl propionate in 16 ml of 1,2-dichlorobenzene are added dropwise to 21.5 g (161 mmol) of aluminum trichloride in 16 ml of 1,2-dichlorobenzene and the mixture is subsequently stirred at 100° C. for 6 hours. It is cooled, diluted with dichloromethane and poured cautiously onto a mixture of 2 M hydrochloric acid and ice. The phases are separated, extraction is carried out with dichloromethane and the extracts are washed with saturated sodium chloride solution and dried over sodium sulphate. The crude product is purified by column chromatography on silica gel (hexane/ethyl acetate 10-20%) to give 21.5 g of 1-(3,4-difluoro-2-hydroxyphenyl)propan-1-one. 21.4 g (115 mmol) of 1-(3,4-difluoro-2-hydroxyphenyl)propan-1-one are dissolved in 170 ml of acetone, and the solution is admixed with 29.5 g of potassium carbonate and 13 ml (209 mmol) of methyl iodide. The mixture is boiled under reflux for 4 hours and stirred at room temperature for 12 hours and then the solvent is largely removed. The residue is poured into water and subjected to extraction with diethyl ether. The extracts are washed with water, dried over sodium sulphate and, following the removal of the solvent in vacuo, give 21.2 g of 1-(3,4-difluoro-2-methoxyphenyl)propan-1-one.

Workup

  1. temperatureIt is cooled
  2. customThe phases are separated
  3. extractionextraction
  4. washthe extracts are washed with saturated sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. customThe crude product is purified by column chromatography on silica gel (hexane/ethyl acetate 10-20%)

Sources & evidence

ORD record
ord-583c5aa8d1fb40a3a4c8a539c712b09f
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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