Water → 2-(3,5-Bis-trifluoromethyl-benzoylamino)-4-hydroxy-benzoic acid methyl ester

HRID 29669Notes

Reaction equation

HRID 29669 reaction equation
[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7](N)=[CH:6][C:5]=1[NH:11][C:12](=[O:27])[C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15]([C:23]([F:26])([F:25])[F:24])[CH:14]=1.N([O-])=[O:30].[Na+].S(=O)(=O)(O)O.O>FC(F)(F)C(O)=O>[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([OH:30])=[CH:6][C:5]=1[NH:11][C:12](=[O:27])[C:13]1[CH:14]=[C:15]([C:23]([F:24])([F:26])[F:25])[CH:16]=[C:17]([C:19]([F:22])([F:20])[F:21])[CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1118Sulfuric Acid3×HCID 23668193Sodium NitriteHCID 865973994-Amino-2-(3,5-bis-trifluoromethyl-benzoylamino)-benzoic acid methyl ester

Product 1

HCID 865974002-(3,5-Bis-trifluoromethyl-benzoylamino)-4-hydroxy-benzoic acid methyl esterYield 76.4%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent2×

Procedure

To a solution of 4-amino-2-(3,5-bis-trifluoromethyl-benzoylamino)-benzoic acid methyl ester (1.70 g, 4.18 mmol) in trifluoroacetic acid (25 mL) which has been cooled to 0° C. was slowly added a solution of sodium nitrite (0.35 g, 5.06 mmol in 9 mL of water). In a separate flask, concentrated sulfuric acid (21 m]L) was added to water (50 mL) to make a 30% sulfuric acid solution. After 5 minutes, the trifluoroacetic acid mixture was slowly added to the sulfuric acid solution. After complete addition, the reaction mixture was allowed to stir at ambient temperature for 15 minutes. The reaction mixture was extracted with three portions of ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography through silica gel using ethyl acetate/hexanes (20/80) to give 2-(3,5-bis-trifluoromethyl-benzoylamino)-4-hydroxy-benzoic acid methyl ester (1.30 g, 76%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6); δ 11.92 (s, 1H), 10.68 (s, 1H), 8.50 (s, 2H), 8.44 (s, 1H), 8.03 (d, 1H), 7.88 (d, 1H), 6.64 (dd, 1H), 3.84 (s, 3H).

Workup

  1. additionAfter complete addition
  2. extractionThe reaction mixture was extracted with three portions of ethyl acetate
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by flash chromatography through silica gel

Sources & evidence

ORD record
ord-41d5020f01a947588c037674d804825d
Source dataset
uspto-grants-2008_09
Patent number
US07420083B2

Reaction notes

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