Benzocaine → Ethyl 4-(piperazin-1-yl)benzoate

HRID 2290440Notes

Reaction equation

HRID 2290440 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.Cl.Cl[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]Cl.C(=O)([O-])[O-].[K+].[K+]>C(O)CCC>[N:1]1([C:2]2[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][CH:12]=2)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 2337BenzocaineHCID 11430Potassium CarbonateHCID 522769Bis(2-chloroethyl)amine hydrochloride

Product 1

HCID 2761178Ethyl 4-(piperazin-1-yl)benzoate

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 39.5 g. (0.24 mole) ethyl 4-aminobenzoate (free base), 140 ml. n-butanol and 47.1 g. (0.265 mole) bis-(2-chloroethyl)-amine hydrochloride is heated at reflux temperature for 36 hours, then 16.8 g. (0.12 mole) powdered anhydrous potassium carbonate are added thereto followed by further heating for 80 hours. The hot reaction mixture is then suction filtered, the filter cake is washed with some hot butanol and the combined filtrates are cooled. After standing overnight, the solid product obtained is filtered off with suction, washed twice with 50 ml. amounts of diethyl ether and dried. Yield: 33.4 g. (64% of theory) of yellow crystals which are recrystallised from ethanol/diethyl ether (2:1 v/v) to give 28.45 g. (55% of theory) of the desired product in the form of an almost colourless hydrochloride; m.p. 176°-178° C. The product is hydroscopic.

Workup

  1. additionA mixture of 39.5 g
  2. temperatureat reflux temperature for 36 hours
  3. additionare added
  4. temperatureby further heating for 80 hours
  5. filtrationsuction filtered
  6. washthe filter cake is washed with some hot butanol
  7. temperaturethe combined filtrates are cooled
  8. customthe solid product obtained
  9. filtrationis filtered off with suction
  10. washwashed twice with 50 ml
  11. dry with materialamounts of diethyl ether and dried
  12. custom(64% of theory) of yellow crystals which are recrystallised from ethanol/diethyl ether (2:1 v/v)
  13. customto give 28.45 g

Sources & evidence

ORD record
ord-646c99a840e34fa28ea0da286c6817d3
Source dataset
uspto-grants-1986_10
Patent number
US04616086

Reaction notes

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