4-Chloro-2-fluoro-5-methoxy-alpha-methylbenzenemethanol → 1-(4-Chloro-2-fluoro-5-methoxyphenyl)ethanone

HRID 1450022Notes

Reaction equation

HRID 1450022 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([CH:10]([CH3:12])[OH:11])=[C:4]([F:13])[CH:3]=1.CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O.O>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10](=[O:11])[CH3:12])=[C:4]([F:13])[CH:3]=1

Participants

5

Reactant 2

HCID 233528504-Chloro-2-fluoro-5-methoxy-alpha-methylbenzenemethanolHCID 131709961Jones' reagent

Product 1

HCID 233528781-(4-Chloro-2-fluoro-5-methoxyphenyl)ethanoneYield 90.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

A stirred solution of 10.4 g of 4-chloro-2-fluoro-5-methoxybenzaldehYde in 150 mL of anhydrous THF was cooled in a dry ice-acetone bath and treated with 35 mL of a 3M solution of methyl magnesium chloride in THF over a period of one minute. The ice bath was removed and the mixture allowed to warm to room temperature. After warming, the solution was slowly poured into ice water. The water slurry was extracted three times with diethyl ether, the ether extracts dried and concd to afford a crude oil. Crystallization from hexanes yielded 10.8 g (95.6%) of 4-chloro-2-fluoro-5-methoxy-α-methylbenzenemethanol: mp 68.5°-69.5° C. This benzenemethanol intermediate was dissolved in 100 mL of acetone, cooled in an ice water bath and treated dropwise with 50 mL of freshly prepared Jones' reagent (prepared from 6.7 g of CrO3, 6 mL of H2SO4 and 50 mL of water), keeping the temperature below 10° C. After stirring for 2 hrs, the solution was diluted with water and extracted three times with methylene chloride. The organic extracts were dried and concd to give a crude product. Recrystallization from methanol yielded 9.66 g (90.3%) of 1-(4-chloro-2-fluoro-5-methoxyphenyl)ethanone as a white solid: mp 96.5°-98.5° C.; 1HNMR (CDCl3) δ2.50 (d, 3H, 5.4 Hz), 3.80 (s, 3H), 7.10 (d, 1H, 10.1 Hz), 7.30 (d, 1H, 6.3 Hz).

Workup

  1. temperaturecooled in an ice water bath
  2. customthe temperature below 10° C
  3. extractionextracted three times with methylene chloride
  4. customThe organic extracts were dried
  5. customto give a crude product
  6. customRecrystallization from methanol

Sources & evidence

ORD record
ord-f6634d6d46fb48edaf33d9dca1ca3d2b
Source dataset
uspto-grants-1997_02
Patent number
US05600016

Reaction notes

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