Ammonia → 4-(Chloromethyl)-2-(4-isopropoxyphenyl)-5-methyl-1,3-oxazole

HRID 1394675Notes

Reaction equation

[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]([CH3:18])=[C:14]([CH3:17])[N+:15]=2[O-])=[CH:7][CH:6]=1)([CH3:3])[CH3:2].Cl.P(Cl)(Cl)([Cl:22])=O.N>C(Cl)(Cl)Cl>[Cl:22][CH2:17][C:14]1[N:15]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:6][CH:7]=2)[O:12][C:13]=1[CH3:18]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-(4-isopropoxy-phenyl)-4,5-dimethyl-oxazole 3-oxide; hydrochloride (2.5 g, 8.8 mmol) in chloroform (12 ml) was added a solution of phosphorous oxychloride (1 ml, 11 mmol) in chloroform (12 ml) within 5 min. The reaction mixture was heated under reflux for 45 min, cooled to 0° C. and made basic (pH 10) by carefully adding concentrated aqueous NH3 solution. The suspension was poured onto ice water and extracted two times with dichloromethane. The combined extracts were washed with ice water/brine and dried over sodium sulfate. Removal of the solvent under reduced pressure gave a brown oil which was purified by column chromatography (silica gel, dichloromethane) to yield 1.6 g (6 mmol, 60%) of the title compound as colorless oil.

Workup

temperatureThe reaction mixture was heated
temperatureunder reflux for 45 min
additionThe suspension was poured onto ice water
extractionextracted two times with dichloromethane
washThe combined extracts were washed with ice water/brine
dry with materialdried over sodium sulfate
customRemoval of the solvent under reduced pressure
customgave a brown oil which
customwas purified by column chromatography (silica gel, dichloromethane)

Sources & evidence

ORD record: ord-6a0d786eefae4df492ad603a8467d45c
Source dataset: uspto-grants-2008_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07348349B2

Reaction notes

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