Acetic Anhydride → 2-Acetylamino-3,4,5,6-tetrafluorobenzoic acid

HRID 2372042Notes

Reaction equation

HRID 2372042 reaction equation
[F:1][C:2]1[C:10]([F:11])=[C:9]([F:12])[C:8]([F:13])=[C:4]([C:5]([OH:7])=[O:6])[C:3]=1[NH2:14].[C:15](OC(=O)C)(=[O:17])[CH3:16]>C(O)(=O)C>[C:15]([NH:14][C:3]1[C:2]([F:1])=[C:10]([F:11])[C:9]([F:12])=[C:8]([F:13])[C:4]=1[C:5]([OH:7])=[O:6])(=[O:17])[CH3:16]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 6881852-Amino-3,4,5,6-tetrafluorobenzoic acid

Product 1

HCID 199057552-Acetylamino-3,4,5,6-tetrafluorobenzoic acid

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

The general pathway to the compounds of formula IV is illustrated with 2-nitro-3,4,5,6-tetrafluorobenzoyl chloride. This starting material is treated with n-butyl lithium and malonic half acid ester to form 2-nitro-3,4,5,6-tetrafluoro-β-oxo-benzene propanoic acid ethyl ester. This product can be converted to 5-nitro-1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid ethyl ester by a three step reaction. The starting material is first treated with triethylorthoformate and subsequently with cyclopropyl amine in t-butyl alcohol. The product is ring closed with potassium t-butoxide to form 5-nitro-1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl ester. This product is hydrogenated to form the corresponding 5-amino compound. This is then hydrolyzed to form 1-cyclopropyl-5-amino-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid. Alternatively compounds of the formula IV may be prepared by a series of reactions illustrated with 3,4,5,6-tetrafluoroanthranilic acid. The acid is reacted with acetic anhydride and acetic acid to form 2-acetylamino-3,4,5,6-tetrafluorobenzoic acid. This compound is reacted with oxalyl chloride and dichloromethane in the presence of N,N-dimethylformamide catalyst to form 2-acetylamino-3,4,5,6-tetrafluorobenzoyl chloride. This product is treated with n-butyl lithium and malonic half acid ester to form 2-acetylamino-3,4,5,6-tetrafluoro-β-oxobenzenepropanoic acid ethyl ester.

Sources & evidence

ORD record
ord-f751c594f15b4c7daf04bf1e517281ae
Source dataset
uspto-grants-1992_03
Patent number
US05097032

Reaction notes

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