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

HRID 1387357Notes

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-tetrahydro-pyranyloxymethyl)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-c9c76aefc0fa42b1b3e7b69bf98e8950
Source dataset: uspto-grants-2001_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06268312B1

Reaction notes

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