Ethyl Bromide → 2-(2,5-Dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl ketone

HRID 279444Notes

Reaction equation

HRID 279444 reaction equation
BrCC.[Mg].Br[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][O:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=1[CH3:21].[CH3:22][C:23]1[CH:27]=[C:26]([C:28](Cl)=[O:29])[O:25][N:24]=1.[Cl-].[NH4+]>C1COCC1>[CH3:22][C:23]1[CH:27]=[C:26]([C:28]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[CH2:12][O:13][C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=2[CH3:21])=[O:29])[O:25][N:24]=1

Participants

7

Reactant 5

HCID 6332Ethyl BromideHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 109462162-Bromobenzyl-(2,5-dimethylphenyl)etherHCID 129050993-Methyl-1,2-oxazole-5-carbonyl chloride

Product 1

HCID 226246042-(2,5-Dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl ketoneYield 17.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

THF (2 ml) and bromoethane (0.1 ml) were added to magnesium (0.49 g, 0.02 mol) in a stream of nitrogen, and the mixture was stirred at 50° C. for 10 minutes. Then, a mixture of 1-bromo-2-(2,5-dimethylphenoxymethyl)benzene (2.91 g, 0.01 mol) and THF (8 ml) was added at 50 to 60° C. over 30 minutes, and the mixture was stirred at 50 to 60° C. for 1 hour. After completion of the reaction, the reaction mixture was added to a mixture of 3-methylisoxazol-5-carbonyl chloride (1.45 g, 0.01 mol) and THF (15 ml) at −70 to −60° C. over 15 minutes, and then the mixture was stirred at −70 to −60° C. for 0.5 hours. After completion of the reaction, saturated aqueous ammonium chloride solution (150 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl ketone (0.56 g, 17.4%) as colorless crystals. mp. 106-108° C.

Workup

  1. additionwas added at 50 to 60° C. over 30 minutes
  2. stirringthe mixture was stirred at 50 to 60° C. for 1 hour
  3. customAfter completion of the reaction
  4. stirringthe mixture was stirred at −70 to −60° C. for 0.5 hours
  5. additionwas added
  6. extractionthe mixture was extracted with ether
  7. dry with materialThe ether layer was dried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customthe residue was purified by silica gel chromatography (ethyl acetate/n-hexane)
  10. customrecrystallized from n-hexane

Sources & evidence

ORD record
ord-0399aae327c8436abd79c6c6f70781c9
Source dataset
uspto-grants-2002_03
Patent number
US06362212B1

Reaction notes

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