Benzocaine → 4-(1H-1,2,3,4-tetrazol-1-yl)benzoic acid

HRID 68786Notes

Reaction equation

HRID 68786 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.[CH2:13](OC(OCC)OCC)C.[N-:23]=[N+:24]=[N-:25].[Na+]>C(O)(=O)C>[N:1]1([C:2]2[CH:12]=[CH:11][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=2)[CH:13]=[N:25][N:24]=[N:23]1

Participants

5

Reactant 3

HCID 2337BenzocaineHCID 31214Ethyl orthoformateHCID 33557Sodium Azide

Product 1

HCID 6741614-(1H-1,2,3,4-tetrazol-1-yl)benzoic acid

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of ethyl 4-aminobenzoate (1.65 g) in acetic acid (20 mL) is added triethylorthoformate (8 mL) and sodium azide (1.17 g) and the solution is heated at reflux for 4 h. After cooling and removing acetic acid in vacuo, water and dichloromethane are added and the organic layer is separated and dried (MgSO4) and concentrated. The crude ester is dissolved in methanol (30 mL) and 4 M aqueous NaOH solution (3 mL) is added and the solution is stirred at room temperature for 2 h. The mixture is neutralized with 6 M aqueous HCl, concentrated and then acidified with 6 M aqueous HCl. The precipitate is filtered off washing with water and dried by suction to give the title compound.

Workup

  1. temperaturethe solution is heated
  2. temperatureat reflux for 4 h
  3. temperatureAfter cooling
  4. customremoving acetic acid in vacuo, water and dichloromethane
  5. additionare added
  6. customthe organic layer is separated
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. dissolutionThe crude ester is dissolved in methanol (30 mL)
  10. addition4 M aqueous NaOH solution (3 mL) is added
  11. concentrationconcentrated
  12. filtrationThe precipitate is filtered off
  13. washwashing with water
  14. customdried by suction

Sources & evidence

ORD record
ord-923db62779d043b4a03f4aef670841ea
Source dataset
uspto-grants-2014_09
Patent number
US08822471B2

Reaction notes

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