Methanol → Methyl 2-Amino-4-(trifluoromethyl)benzoate

HRID 1441525Notes

Reaction equation

HRID 1441525 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(=O)(=O)(O)O.[CH3:20]O>>[CH3:20][O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][C:9]([C:11]([F:12])([F:13])[F:14])=[CH:10][C:2]=1[NH2:1]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 678694-(Trifluoromethyl)anthranilic acid

Product 1

HCID 12601886Methyl 2-Amino-4-(trifluoromethyl)benzoateYield 75%

Procedure

To a solution of 2-amino-4-trifluoromethyl-benzoic acid (72.0 g, 351 mmol) in MeOH (1000 mL) was added dropwise concentrated sulfuric acid (50 mL). The mixture was heated to reflux for 16 h under nitrogen, allowed to cool to r.t., and then concentrated in vacuo to ¼ of its volume. The mixture was taken up in EtOAc and washed with water, 10% aqueous solution of sodium carbonate, and brine. It was then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by column chromatography (silica gel 60, hexanes/EtOAc 9:1) furnished 2-amino-4-trifluoromethyl-benzoic acid methyl ester (57.8 g, 264 mmol, 75%) as a white powder, m.p. 59° C., ESI-MS: m/z 218 [M−H]−.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 16 h under nitrogen
  3. concentrationconcentrated in vacuo
  4. washwashed with water, 10% aqueous solution of sodium carbonate, and brine
  5. dry with materialIt was then dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography (silica gel 60, hexanes/EtOAc 9:1)

Sources & evidence

ORD record
ord-5b3f98fb02504c6f9ed4cceeef905c06
Source dataset
uspto-grants-2010_02
Patent number
US07655666B2

Reaction notes

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