Benzocaine → ethyl 4-(methylamino)benzoate

HRID 131281Notes

Reaction equation

HRID 131281 reaction equation
[NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH:13](OCC)(OCC)OCC.FC(F)(F)C(O)=O>>[CH3:13][NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][CH:12]=1

Participants

4

Reactant 3

HCID 2337BenzocaineHCID 6422Trifluoroacetic acidHCID 31214Ethyl orthoformate

Product 1

HCID 319832ethyl 4-(methylamino)benzoateYield 46.5%

Procedure

A mixture of ethyl p-aminobenzoate (25.2 g), triethyl orthoformate (80 g) and trifluoroacetic acid (0.2 mL) is refluxed under heating for 3 hours. After cooling, the reaction mixture is concentrated in vacuo and the residue is subjected to azeotropic distillation with ethanol. The residue is suspended in ethanol (400 mL) and thereto is added sodium borohydride (23 g), and the mixture is refluxed under heating for 3 hours. After cooling, to the reaction mixture is added ethyl acetate and water. The mixture is stirred at room temperature for 1 day. The organic layer is separated, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue is purified by flash column chromatography on silica gel (Solvent; n-hexane:ethyl acetate=4:1) to give ethyl 4-(methylamino)benzoate (12.7 g, yield; 46%) as a pale yellow amorphous powder. MS (APCI) m/z: 180 [M+H]+

Workup

  1. temperatureis refluxed
  2. temperatureunder heating for 3 hours
  3. temperatureAfter cooling
  4. concentrationthe reaction mixture is concentrated in vacuo
  5. distillationthe residue is subjected to azeotropic distillation with ethanol
  6. additionis added sodium borohydride (23 g)
  7. temperaturethe mixture is refluxed
  8. temperatureunder heating for 3 hours
  9. temperatureAfter cooling, to the reaction mixture
  10. additionis added ethyl acetate and water
  11. customThe organic layer is separated
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe residue is purified by flash column chromatography on silica gel (Solvent; n-hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-853a5d7c97b146f192ea38a022e62efb
Source dataset
uspto-grants-2008_06
Patent number
US07384952B2

Reaction notes

Loading…