Aniline → Methyl 4-amino-3-fluoro-5-nitro-2-(phenylamino)benzoate

HRID 31968Notes

Reaction equation

HRID 31968 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.[NH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[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:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

3

Reactant 2

HCID 6115AnilineHCID 2759749Benzoic acid, 4-amino-2,3-difluoro-5-nitro-, methyl ester2×

Product 1

HCID 44122658Methyl 4-amino-3-fluoro-5-nitro-2-(phenylamino)benzoate

Conditions

Temperature
125 °C

Procedure

4-Amino-2,3-difluoro-5-nitro-benzoic acid methyl ester 4 (23.48 g, 101.1 mmol), the product of Example 1, Step C, is suspended in xylenes (125 mL) and aniline (92 mL, 1011 mmol) is added. The reaction mixture is stirred at 125° C. for 16 hours under N2. The reaction mixture is cooled to room temperature and solids precipitate out of solution. The solids are collected by filtration and are washed with xylenes and then diethyl ether. Recovered 22.22 g (72.78 mmol) of yellow solid which is pure desired product. The filtrate is concentrated under reduced pressure, redissolved in methylene chloride and flushed through a plug of silica gel eluting with methylene chloride. The desired fractions are concentrated under reduced pressure to give a brown solid which is triturated with diethyl ether to give 5.47 g (17.91 mmol) of yellow solid which is pure desired product. Combined product yield is 27.69 g (90%). MS APCI (−) m/z 304 (M−1) detected.

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. customsolids precipitate out of solution
  3. filtrationThe solids are collected by filtration
  4. washare washed with xylenes

Sources & evidence

ORD record
ord-5d31eafa4d994c0185b7ff95fae6cef9
Source dataset
uspto-grants-2008_09
Patent number
US07425637B2

Reaction notes

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