Hydrogen Peroxide → 2-Amino-4,5-difluorobenzoic acid
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7]C(=O)[C:5]2=[O:13].[OH:14]O>>[NH2:7][C:8]1[CH:9]=[C:10]([F:11])[C:2]([F:1])=[CH:3][C:4]=1[C:5]([OH:13])=[O:14]Participants
Procedure
In accordance with the above reaction scheme, an aqueous solution of 3,4-difluoroaniline (I) and hydroxylamine hydrochloride containing hydrochloric acid is reacted with an aqueous solution of chloral hydrate and sodium sulfate at the reflux, then filtered while hot, giving N-(3,4-difluorophenyl)-2-(hydroxyimino)-acetamide (II). The compound (II) is reacted with concentrated sulfuric acid with heat, then added to cracked ice, giving 5,6-difluoro-1H-indole-2,3-dione (III). A basic aqueous solution of compound (III) is treated with hydrogen peroxide and heat, then cooled and acidified, giving 2-amino-4,5-difluorobenzoic acid (IV). The compound (IV) is added to a mixture of anhydrous copper(II) chloride, t-butyl nitrite and anhydrous acetonitrile at 0°-5° C., then added to a dilute mineral acid, giving 2-chloro-4,5-difluorobenzoic acid (V).
Workup
- temperatureheat
- temperaturecooled
Sources & evidence
- ORD record
- ord-592c2572923943fa8c221c609b548fc9
- Source dataset
- uspto-grants-1989_05
- Patent number
- US04833270
Reaction notes
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