2-Fluoroaniline → Methyl 4-amino-3-fluoro-2-((2-fluorophenyl)amino)-5-nitrobenzoate

HRID 2104004Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[C:7]([NH2:13])=[C:6]([F:14])[C:5]=1F.[F:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[NH2:24]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[C:7]([NH2:13])=[C:6]([F:14])[C:5]=1[NH:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[F:17]

Participants

Conditions

Temperature: 140 °C

Procedure

4-Amino-2,3-difluoro-5-nitro-benzoic acid methyl ester 4 (1.50 g, 6.46 mmol) is suspended in xylenes (7.5 mL) and 2-fluoro-phenylamine (6.24 mL, 64.6 mmol) is added. The reaction mixture is stirred at 140° C. under N2. After stirring for 6 days, the reaction is complete. The reaction mixture is cooled to room temperature and diluted with methylene chloride and filtered through a silica gel plug eluting with methylene chloride (1 L) to give an orange filtrate. The filtrate is concentrated to dryness and then triturated with diethyl ether to yield a bright yellow solid. The trituration is repeated. The yellow solid is collected to yield 1.08 g (52%) of the pure desired product. MS APCI (−) m/z 322 (M−1) detected.

Workup

stirringAfter stirring for 6 days
temperatureThe reaction mixture is cooled to room temperature
filtrationfiltered through a silica gel plug
washeluting with methylene chloride (1 L)
customto give an orange filtrate
concentrationThe filtrate is concentrated to dryness
customtriturated with diethyl ether
customto yield a bright yellow solid
customThe yellow solid is collected

Sources & evidence

ORD record: ord-89e50d80bdb44b8482f2d16ba9b7645a
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07576114B2

Reaction notes

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