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

HRID 1767784Notes

Reaction equation

HRID 1767784 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-fafdc251b4384622afc08751d8e94903
Source dataset
uspto-grants-2007_06
Patent number
US07235537B2

Reaction notes

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