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

HRID 279473Notes

Reaction equation

[Mg].BrCC.Br[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][O:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][O:15]1.CON(C)[C:23]([C:25]1[O:29][N:28]=[C:27]([CH3:30])[CH:26]=1)=[O:24]>O.C1COCC1>[CH3:30][C:27]1[CH:26]=[C:25]([C:23]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[CH2:12][O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)=[O:24])[O:29][N:28]=1

Participants

Conditions

Temperature: 55 °C

Procedure

Magnesium (0.73 g, 0.03 mol) and bromoethane (0.2 ml) were added to a mixture of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (5.42 g, 0.02 mol) and THF (50 ml) under an atmosphere of nitrogen gas, and the resulting mixture was stirred at 50 to 60° C. for 1 hour to prepare Grignard reagent. The Grignard reagent was added dropwise to a mixture of N-methoxy-3, N-dimethyl-5-isoxazolcarboxamide (3.40 g, 0.02 mol) and THF (40 ml). The mixture was stirred at −60° C. to room temperature for 1 hour, water (200 ml) was added, and the mixture was extracted with ether (200 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone (4.09 g, yield: 67.9%) as a colorless oil.

Workup

stirringThe mixture was stirred at −60° C. to room temperature for 1 hour
extractionthe mixture was extracted with ether (200 ml)
dry with materialThe extract was dried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography (ethyl acetate/n-hexane)

Sources & evidence

ORD record: ord-c0b90c5ccde6417c9a44943d55dd3f3e
Source dataset: uspto-grants-2002_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06362212B1

Reaction notes

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