Benzocaine → 4-[(2-Phenylethyl)amino]benzoic acid

HRID 1703072Notes

Reaction equation

HRID 1703072 reaction equation
[NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][CH:3]=1.Br[CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.CN(C)P(N(C)C)(N(C)C)=O>O>[CH2:14]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([OH:8])=[O:7])=[CH:11][CH:12]=1)[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 2337BenzocaineHCID 7666Phenethyl bromideHCID 12679Hexamethylphosphoramide

Product 1

HCID 130796554-[(2-Phenylethyl)amino]benzoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-20 °C

Procedure

A mixture of 16.5 g. of ethyl p-aminobenzoate, 10.3 g. of (2-bromoethyl)benzene and 50 ml. of hexamethylphosphoramide is heated in an oil bath at 115°-120° C. for 17 hours. The mixture is put into ice and water and extracted with ether. The ether extracts are washed with water, dried over magnesium sulfate and concentrated in vacuo to an oil. The oil is combined with 200 ml. of ethanol-water (9:1) and 20 g. of potassium hydroxide and the mixture is refluxed for 3.5 hours. After chilling the mixture is made acidic with concentrated hydrochloric acid, diluted with 150 ml. of water, chilled, diluted with water and extracted with chloroform. The chloroform extracts are washed with water, dried over magnesium sulfate and concentrated in vacuo to a gum. Ethanol is added, the mixture is chilled and filtered to give yellow crystals. The mother liquors are chilled at -20° C. to give a second crop of crystals. Recrystallization of the combined crops of crystals from hexane-ethanol gives yellow crystals, m.p. 123°- 125° C. Recrystallization from ethanol gives pale yellow crystals, m.p. 124°-126° C.

Workup

  1. additionA mixture of 16.5 g
  2. extractionextracted with ether
  3. washThe ether extracts are washed with water
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo to an oil
  6. temperatureof potassium hydroxide and the mixture is refluxed for 3.5 hours
  7. temperatureAfter chilling the mixture
  8. additiondiluted with 150 ml
  9. temperatureof water, chilled
  10. additiondiluted with water
  11. extractionextracted with chloroform
  12. washThe chloroform extracts are washed with water
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated in vacuo to a gum
  15. additionEthanol is added
  16. temperaturethe mixture is chilled
  17. filtrationfiltered
  18. customto give yellow crystals
  19. customto give a second crop of crystals
  20. customRecrystallization of the combined crops of crystals from hexane-ethanol
  21. customgives yellow crystals, m.p. 123°- 125° C
  22. customRecrystallization from ethanol
  23. customgives pale yellow crystals, m.p. 124°-126° C.

Sources & evidence

ORD record
ord-c05a301ddb0f40bc8e2294f0440f2e1a
Source dataset
uspto-grants-1982_09
Patent number
US04350822

Reaction notes

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