Hydrochloric Acid → Benzyl piperazine-1-carboxylate

HRID 542847Notes

Reaction equation

HRID 542847 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Cl.[CH2:8]([O:15][C:16](Cl)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[OH-].[Na+]>CO.O>[N:1]1([C:16]([O:15][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:17])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 4837PiperazineHCID 10387Benzyl chloroformateHCID 14798Sodium Hydroxide

Product 1

HCID 643495Benzyl piperazine-1-carboxylateYield 48.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of 17.2 g (0.2 mole) of anhydrous piperazine, 40 ml of water and 60 ml (0.36 mole) of 6N hydrochloric acid in 300 ml of methanol was heated to boiling. Small portions of benzylchloroformate (total 48 g, 0.28 mole) and 4N sodium hydroxide (total 100 ml) were added alternately to maintain a pH of 4.5-5.5. The mixture was heated under reflux for 3 hr, allowed to cool overnight, concentrated in vacuo to remove the methanol, made alkaline with sodium hydroxide and extracted with dichloromethane. The dichloromethane extract was washed with water and then extracted with 400 ml of 1N hydrochloric acid. The acid extract was washed with dichloromethane, made alkaline with sodium hydroxide, and extracted with dichloromethane. The dichloromethane extract was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness in vacuo to give 25 g of crude product. Distillation under vacuum afforded 21.3 g (48%) of the product, bp 140°-143° (0.1 torr). VPC indicated the material consisted of 97% of a single component and the NMR was consistent with the assigned structure.

Workup

  1. temperaturewas heated to boiling
  2. temperatureto maintain a pH of 4.5-5.5
  3. temperatureThe mixture was heated
  4. temperatureunder reflux for 3 hr
  5. temperatureto cool overnight
  6. concentrationconcentrated in vacuo
  7. customto remove the methanol
  8. extractionextracted with dichloromethane
  9. extractionThe dichloromethane extract
  10. washwas washed with water
  11. extractionextracted with 400 ml of 1N hydrochloric acid
  12. extractionThe acid extract
  13. washwas washed with dichloromethane
  14. extractionextracted with dichloromethane
  15. extractionThe dichloromethane extract
  16. washwas washed with water
  17. dry with materialdried over anhydrous magnesium sulfate
  18. filtrationfiltered
  19. concentrationconcentrated to dryness in vacuo
  20. customto give 25 g of crude product
  21. distillationDistillation under vacuum

Sources & evidence

ORD record
ord-8395b8182b7d4ff0b10839235dccbe08
Source dataset
uspto-grants-1987_04
Patent number
US04659708

Reaction notes

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