p-Toluenesulfonic acid → Ethyl 2-amino-4-(trifluoromethyl)benzoate

HRID 1439764Notes

Reaction equation

HRID 1439764 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([NH2:12])[C:6](=[CH:10][CH:11]=1)[C:7]([OH:9])=[O:8].[C:15]1(C)C=CC(S(O)(=O)=O)=C[CH:16]=1.S([O-])([O-])(=O)=O.[Mg+2]>C(O)C.C1(C)C=CC=CC=1>[CH2:15]([O:8][C:7](=[O:9])[C:6]1[C:5](=[CH:4][C:3]([C:2]([F:13])([F:14])[F:1])=[CH:11][CH:10]=1)[NH2:12])[CH3:16]

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 24083Sulfuric acid magnesium salt (1:1)HCID 678694-(Trifluoromethyl)anthranilic acid

Product 1

HCID 12800885Ethyl 2-amino-4-(trifluoromethyl)benzoate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

19.8 grams of 4-trifluoromethylanthranilic acid are dissolved in 350 ml of anhydrous ethanol and 300 ml of dry toluene. To this solution is added 21.8 grams of anhydrous p-toluenesulfonic acid. The solution is refluxed under an extractor containing a thimble of anhydrous magnesium sulfate for 2 weeks with periodic replacement of the drying agent. The solvent is then removed on a rotary evaporator. The residue is treated with 200 ml of 2N sodium hydroxide. The resultant mixture is extracted thrice with combined 75 ml portions of diethylether. The combined extracts are washed with 2N sodium hydroxide, then distilled water and finally brine. The organic solution is dried over anhydrous potassium carbonate. The drying agent is filtered off, and the solvent is removed on a rotary evaporator. The resultant oil is chromatographed on a filter column of silica gel with chloroform as the eluant. The first fractions contain 4-trifluoromethylanthranilic acid ethyl ester, which is recovered by crystallization. Melting Point: 42°-43° C.

Workup

  1. temperatureThe solution is refluxed under an extractor
  2. customThe solvent is then removed on a rotary evaporator
  3. additionThe residue is treated with 200 ml of 2N sodium hydroxide
  4. extractionThe resultant mixture is extracted thrice with combined 75 ml portions of diethylether
  5. washThe combined extracts are washed with 2N sodium hydroxide
  6. dry with materialThe organic solution is dried over anhydrous potassium carbonate
  7. filtrationThe drying agent is filtered off
  8. customthe solvent is removed on a rotary evaporator
  9. customThe resultant oil is chromatographed on a filter column of silica gel with chloroform as the eluant
  10. customis recovered by crystallization

Sources & evidence

ORD record
ord-4f988d62740f43c09000b671ac7e59e1
Source dataset
uspto-grants-1977_11
Patent number
US04060638

Reaction notes

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