Benzyl chloroformate → Benzyl 4-oxopiperidine-1-carboxylate

HRID 358389Notes

Reaction equation

HRID 358389 reaction equation
C([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)C1C=CC=CC=1.Cl[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17]>C1(C)C=CC=CC=1.O>[C:16]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17]

Participants

5

Reactant 2

HCID 10387Benzyl chloroformateHCID 192201-Benzyl-4-piperidone

Product 1

HCID 643496Benzyl 4-oxopiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

N-Benzyl-4-piperidone (122.2 g, 0.645 mole) in 500 ml toluene was warmed to 45° C. Benzyl chloroformate (130 ml, 155 g, 0.915 mole) was added in a thin, steady stream, and the reaction mixture heated to reflux for 2 hours, cooled to ambient temperature, diluted with 250 ml H2O and stirred vigorously 0.5 hour. The organic layer was separated, washed 1×400 ml 6N HCl and then 1×100 ml saturated NaCl, dired (MgSO4), treated with activated carbon, and concentrated to an oil. The oil was distributed between 400 ml ethyl acetate and 400 ml of H2O containing 67.0 g NaHSO3, stirred 0.5 hour, and the aqueous layer separated, washed with 3 portions of ether, made basic with aqueous NaOH and extracted with fresh ether. The ether layer was dried and reevaporated to yield purified title product as an oil, 136.1 g.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureto reflux for 2 hours
  3. customThe organic layer was separated
  4. washwashed 1×400 ml 6N HCl
  5. addition1×100 ml saturated NaCl, dired (MgSO4), treated with activated carbon
  6. concentrationconcentrated to an oil
  7. stirringstirred 0.5 hour
  8. customthe aqueous layer separated
  9. washwashed with 3 portions of ether
  10. extractionextracted with fresh ether
  11. dry with materialThe ether layer was dried
  12. customreevaporated
  13. customto yield
  14. custompurified title product as an oil, 136.1 g

Sources & evidence

ORD record
ord-b3dd0c15605d43fcbfa5c561b011d0e2
Source dataset
uspto-grants-1984_08
Patent number
US04467090

Reaction notes

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