4-Fluorobenzonitrile → HCID 178513323, compound
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=C(C(O)C)[O:10][N:9]=2)=[CH:4][CH:3]=1.FC1C=CC(C2N=C(C(=O)C)ON=2)=CC=1.FC1C=CC(C#N)=CC=1.Cl.NO>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[NH:12])[NH:9][OH:10])=[CH:4][CH:3]=1Participants
Procedure
In another embodiment, intermediate compounds 1-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)ethanol and 1-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)ethanone may be prepared as described in Scheme 10D. In this route, 4-fluoro-benzonitrile is reacted with hydroxylamine hydrochloride to provide 4-fluoro-N-hydroxybenzimidamide. In one embodiment, the reaction is performed at refluxing temperatures. In another embodiment, the reaction is performed in the presence of a lower alkyl alcohol such as ethanol, and a base such as sodium hydroxide or potassium hydroxide. The resultant compound is then reacted with 2-hydroxy-propionic acid to provide 1-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)ethanol. In one embodiment, the reaction is performed in the presence of DMSO, DCC, and HOBt. 1-(3-(4-Fluorophenyl)-1,2,4-oxadiazol-5-yl)ethanol is then oxidized to 1-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)ethanone. In one embodiment, the oxidation is performed using manganese dioxide in dioxane.
Sources & evidence
- ORD record
- ord-c5a13c63f4d942b398b0144f51ebc6c7
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09266873B2
Reaction notes
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