Ethanol → 5-Allyl-6a-(2-fluorophenyl)-3,3a,4,6-tetrahydro-1H-pyrrolo[3,4-c]isoxazole
Reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[F:11])=O.[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl.[NH2:19]O.[CH2:21]([OH:23])C>>[CH2:17]([N:12]1[CH2:13][CH:14]2[C:3]([C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[F:11])([NH:19][O:23][CH2:21]2)[CH2:2]1)[CH:16]=[CH2:15]Participants
Procedure
To a solution of 2-bromo-1-(2-fluorophenyl)ethanone (10.0 g, 46.1 mmol) in ethanol (460.8 mL) is added drop wise diallyamine (9.4 g, 96.8 mmol) in ethanol (460.8 mL). The reaction is stirred for 2 hr. Pyridine is then added to the reaction (11.2 mL, 138.2 mmol) followed by the addition of hydroxylamine hydrochloride (4.8 g, 69.1 mmol). The reaction is refluxed for 4 hr and then concentrated to dryness. The residue is dissolved in toluene (230.4 mL) and is refluxed for 8 hr. The mixture is cooled to room temperature and extracted with saturated sodium bicarbonate solution. The aqueous phase is then extracted with DCM. The organic phase is concentrated and the mixture purified by silica gel chromatography eluting with hexane to 1:1 hexane/ethyl acetate to give the title compound (6.6 g, 58%). ES/MS (m/e): 248 (M+H).
Workup
- temperatureThe reaction is refluxed for 4 hr
- concentrationconcentrated to dryness
- dissolutionThe residue is dissolved in toluene (230.4 mL)
- temperatureis refluxed for 8 hr
- extractionextracted with saturated sodium bicarbonate solution
- extractionThe aqueous phase is then extracted with DCM
- concentrationThe organic phase is concentrated
- customthe mixture purified by silica gel chromatography
- washeluting with hexane to 1:1 hexane/ethyl acetate
Sources & evidence
- ORD record
- ord-f999833a102b4fa683b1fea90b241266
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08772282B2
Reaction notes
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