O-Toluidine → Methyl 4-amino-3-fluoro-5-nitro-2-(2-toluidino)benzoate

HRID 1176851Notes

Reaction equation

HRID 1176851 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[C:19]([CH3:24])=[CH:20][CH:21]=[CH:22][CH:23]=1>C(OCC)C>[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][C:19]=1[CH3:24]

Participants

4

Reactant 2

HCID 7242O-ToluidineHCID 2759749Benzoic acid, 4-amino-2,3-difluoro-5-nitro-, methyl ester

Product 1

HCID 22180129Methyl 4-amino-3-fluoro-5-nitro-2-(2-toluidino)benzoateYield 68%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

4-Amino-2,3-difluoro-5-nitro-benzoic acid methyl ester 4 (12.0 g, 51.7 mmol) is suspended in xylenes (60 mL) and ortho-toluidine is added (55.2 mL, 518 mmol). The reaction mixture is heated to reflux with stirring under a nitrogen atmosphere. After 36 hours, the reaction mixture is cooled to room temperature, diluted with diethyl ether and washed with 10% aqueous HCl solution. The aqueous washing are extracted with diethyl ether. The combined organic extracts are concentrated under reduced pressure. The residue is dissolved in methylene chloride and filtered through silica gel in a fritted funnel, rising with methylene chloride. Three fractions are recovered. The first (2 liter) is nearly clean by HPLC. The second (1 liter) and third (1 liter) fraction are only partially pure. The first fraction is concentrated under reduced pressure and triturated with diethyl ether to give 11.2 g (68%) of clean desired product as a bright yellow solid: MS APCI (−) m/z 318 (M−1) detected.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux
  3. washwashed with 10% aqueous HCl solution
  4. washThe aqueous washing
  5. extractionare extracted with diethyl ether
  6. concentrationThe combined organic extracts are concentrated under reduced pressure
  7. dissolutionThe residue is dissolved in methylene chloride
  8. filtrationfiltered through silica gel in a fritted funnel
  9. customThree fractions are recovered
  10. concentrationThe first fraction is concentrated under reduced pressure
  11. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-92c7c913149349168ed4f62636579067
Source dataset
uspto-grants-2010_11
Patent number
US07842816B2

Reaction notes

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