Ethyl chloroformate → Norcyclobenzaprine

HRID 2374821Notes

Reaction equation

HRID 2374821 reaction equation
C(=O)([O-])O.[Na+].[CH3:6][N:7]([CH2:9][CH2:10][CH:11]=[C:12]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[CH:20]=[CH:19][C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]1=2)C.Cl.ClC(OCC)=O.[OH-].[K+]>C(Cl)(Cl)Cl.O.C(O)CCC>[CH:17]1[C:18]2[CH:19]=[CH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:12](=[CH:11][CH2:10][CH2:9][NH:7][CH3:6])[C:13]=2[CH:14]=[CH:15][CH:16]=1

Participants

8

Reactant 4

HCID 10928Ethyl chloroformate2×HCID 14797Potassium HydroxideHCID 22576Cyclobenzaprine HydrochlorideHCID 516892Sodium Bicarbonate

Product 1

HCID 9918Norcyclobenzaprine

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 962WaterSolvent2×HCID 6212ChloroformSolvent

Procedure

20 ml of saturated aqueous sodium hydrogencarbonate solution was added to 2.467 g (7.91 mmol) of cyclobenzaprine hydrochloride in 20 ml of chloroform, and they were stirred at room temperature for 10 minutes. After extracting with chloroform, the organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. 15 ml of toluene was added to the residue, and they were heated at 80° C. 4.0 ml (41.8 mmol) of ethyl chloroformate was added thereto, and they were stirred at 80° C. overnight. 4.0 ml (41.8 mmol) of ethyl chloroformate was added to the reaction mixture, and they were stirred under heating for 2 days. Water was added to the reaction mixture. After extracting with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by the silica gel chromatography (hexane:ethyl acetate=1:1). 11.4 ml of 1-butanol and 1.97 g (35.1 mmol) of powdery potassium hydroxide were added to the obtained product, and they were stirred under heating at 120° C. for 4 hours. The reaction mixture was poured in water at room temperature. After the extraction with chloroform, the organic layer was dried over anhydrous sodium sulfate and then concentrated under reduce pressure to obtain the title compound.

Workup

  1. extractionAfter extracting with chloroform
  2. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. addition15 ml of toluene was added to the residue, and they
  5. temperaturewere heated at 80° C
  6. stirringthey were stirred at 80° C. overnight
  7. stirringwere stirred
  8. temperatureunder heating for 2 days
  9. extractionAfter extracting with ethyl acetate
  10. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by the silica gel chromatography (hexane:ethyl acetate=1:1)
  13. stirringwere stirred
  14. temperatureunder heating at 120° C. for 4 hours
  15. extractionAfter the extraction with chloroform
  16. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-9a02f08ed3ad495ab74632ac4f9e3990
Source dataset
uspto-grants-2008_12
Patent number
US07462630B2

Reaction notes

Loading…