4-Fluorobenzaldehyde → N-[(4-fluorophenyl)methylidene]hydroxylamine
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2C=C(C(O)C)[O:10][N:9]=2)=[CH:4][CH:3]=1.FC1C=CC(C2C=C(C(=O)C)ON=2)=CC=1.FC1C=CC(C=O)=CC=1.Cl.NO>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[N:9][OH:10])=[CH:4][CH:3]=1Participants
Procedure
In a further embodiment, 1-(3-(4-fluorophenyl)-isoxazol-5-yl)ethanol and 1-(3-(4-fluorophenyl)-isoxazol-5-yl)ethanone are prepared according to the methodology and reagents of Scheme 12B. 4-Fluoro-benzaldehyde is reacted with hydroxylamine hydrochloride to provide 4-fluorobenzaldehyde oxime. In one embodiment, the reaction is performed in methanol and sodium carbonate. In another embodiment, the reaction is performed at about room temperature for about 4 hours. The isoxazole ring is then generated by reacting this intermediate with 3-hydroxy-butyne and NCS (about 1.2 equivalents) to provide 1-(3-(4-fluorophenyl)isoxazol-5-yl)ethanol. In one embodiment, this cyclization is performed in dichloromethane at about 40° C. 1-(3-(4-Fluorophenyl)isoxazol-5-yl)ethanol is then oxidized to 14344-fluorophenyl)-isoxazol-5-yl)ethanone using Dess-Martin periodinane. In one embodiment, the reaction is performed in dichloromethane. In another embodiment, the reaction is performed at room temperature for about 16 hours.
Sources & evidence
- ORD record
- ord-bbaae9c990ed4a7cad3ec80221220345
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09266873B2
Reaction notes
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