1,3-Dichloroacetone → 4-(Chloromethyl)-2-(4-fluorophenyl)-1,3-oxazole

HRID 1397338Notes

Reaction equation

[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][CH:3]=1.[Cl:11][CH2:12][C:13]([CH2:15]Cl)=O>CCO.C1COCC1>[Cl:11][CH2:12][C:13]1[N:8]=[C:6]([C:5]2[CH:9]=[CH:10][C:2]([F:1])=[CH:3][CH:4]=2)[O:7][CH:15]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of 4-fluorobenzamide (2.5 g, 17.9 mmol) and 1,3-dichloroacetone (2.7 g, 21.6 mmol) in EtOH-THF (20 mL-10 mL) was heated to 85° C. for 24 h. The reaction mixture was cooled to room temperature and quenched with 10% NaHCO3 solution. The organic product was extracted with EtOAc and the organic layer was washed with H2O and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 6-10% EtOAc in petroleum ether) to afford 4-(chloromethyl)-2-(4-fluorophenyl)oxazole (1.2 g, yield 32%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.07-8.02 (m, 2H), 7.70 (m, 1H), 7.19-7.13 (t, J=8.8 Hz, 2H), 4.58 (m, 2H). MS (ESI) m/z: Calculated for C10H7ClNO: 211.02. found: 212.0 (M+H)+.

Workup

temperatureThe reaction mixture was cooled to room temperature
customquenched with 10% NaHCO3 solution
extractionThe organic product was extracted with EtOAc
washthe organic layer was washed with H2O and brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customThe crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 6-10% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-7b6ee52e5bf24b6db52910d3d38ab423
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901156B2

Reaction notes

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