Hydrochloric Acid → 8-Fluoro-4-methylquinoline
Reaction equation
[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].Cl.[CH:10]([C:12]([CH3:14])=O)=[CH2:11]>C(O)C.O.O.O.O.O.O.[Fe](Cl)(Cl)Cl.[Cl-].[Zn+2].[Cl-]>[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:3]=1[N:4]=[CH:11][CH:10]=[C:12]2[CH3:14]Participants
Conditions
- Temperature
- 60 °C
Procedure
To a solution of 2-fluoroaniline (25 ml) in ethanol (185 ml) was added concentrated hydrochloric acid (21 ml), iron (III) chloride hexahydrate (111 g) and zinc (II) chloride (4.1 g) and the resulting mixture was heated to 60° C. Methyl vinyl ketone (25 ml) was added dropwise over 45 min. then the mixture was refluxed for 2 hrs. The reaction mixture was allowed to cool then evaporated under reduced pressure. The resulting oil was basified to pH 12 with 2M sodium hydroxide solution, filtered through arbocel and then the aqueous was extracted with ethyl acetate (×2). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography over silica, eluting with i-hexane/diethyl ether (3:1) followed by i-hexane/diethyl ether (2:1) to give the sub-title compound as a solid (8.25 g).
Workup
- temperaturethe mixture was refluxed for 2 hrs
- temperatureto cool
- customthen evaporated under reduced pressure
- filtrationfiltered through arbocel
- extractionthe aqueous was extracted with ethyl acetate (×2)
- dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
- filtrationfiltered
- customevaporated under reduced pressure
- customThe residue was purified by column chromatography over silica
- washeluting with i-hexane/diethyl ether (3:1)
Sources & evidence
- ORD record
- ord-34942b22469847ef93fc4322a781827e
- Source dataset
- uspto-grants-2008_06
- Patent number
- US07384951B2
Reaction notes
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