Nitric Acid → 2-Chloro-4-fluoro-5-nitrobenzoic Acid

HRID 48485

Reaction equation

[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[N+:12]([O-])([OH:14])=[O:13].S(=O)(=O)(O)O>Cl>[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]

Participants

Conditions

Temperature: 40 °C

Procedure

First, 50 g (0.29 mol) of 2-chloro-4-fluorobenzoic acid was dissolved in 150 ml of hydrochloric acid at room temperature, to which a mixed acid of 28 ml (0.31 mol) of fuming nitric acid and 56 ml of concentrated sulfuric acid was added dropwise at 35° to 45° C. Then, the solution was stirred at 40° C. for 1 hour and poured into 250 ml of ice-water. The precipitated crystals were collected by filtration and recrystallized from a mixed solution of hexane and ethyl acetate, which afforded 55 g (0.25 mol) of 2-chloro-4-fluoro-5-nitrobenzoic acid. Then, 55 g (0.25 mol) of 2-chloro-4-fluoro-5-nitrobenzoic acid was dissolved in 50 ml of ethyl acetate, to which 33 g (0.28 mol) of thionyl chloride was added, and the mixture was heated under reflux for 3 hours and then allowed to stand for cooling to room temperature. Then, 20 ml of ethanol and 30 g of triethylamine were added under ice cooling, and the mixture was stirred at room temperature for 2 hours. The solvent was distilled out, and the residue was purified by silica gel chromatography, which afforded 57 g (0.23 mol) of ethyl 2-chloro-4-fluoro-5-nitrobenzoate.

Workup

additionwas added dropwise at 35° to 45° C
filtrationThe precipitated crystals were collected by filtration
customrecrystallized from a mixed solution of hexane and ethyl acetate, which

Sources & evidence

ORD record: ord-f5fb7feea6c44a198f4e921881582a71
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06703503B2

Linked notes

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