Potassium Carbonate → Ethyl nipecotate

HRID 1599453Notes

Reaction equation

HRID 1599453 reaction equation
C(C(C(C(O)=O)O)O)(O)=O.[CH2:11]([O:13][C:14]([C@@H:16]1[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]1)=[O:15])[CH3:12].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:11]([O:13][C:14]([CH:16]1[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]1)=[O:15])[CH3:12]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 2733695(R)-(-)-Ethyl Nipecotate Tartrate

Product 1

HCID 98969Ethyl nipecotate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

The organic phase was dried (MgSO4) and the solvent evaporated in vacuo affording a residue which was dissolved in acetone (85 ml). To this solution (R)-3-piperidinecarboxylic acid ethyl ester tartrate (9.0 g, 0.03 mol) and potassium carbonate (7.0 g, 0.051 mol) were added and the mixture was heated at reflux temperature for 16 h. After cooling to room temperature and filtration on filter aid (celite) the solvent was removed by evaporation. The residue was dissolved in diethyl ether (100 ml) and extracted with a 5% tartaric acid solution (3×125 ml). The combined aqueous extracts were washed with diethyl ether and pH was adjusted to 7-8 with a potassium carbonate solution. The neutralised aqueous mixture was extracted with ethyl acetate (4×200 ml). The combined ethyl acetate extracts were washed with water, brine and dried (MgSO4). The solvent was evaporated in vacuo affording 2.6 g (32%) of 1-(4-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-1-butyl!-3-piperidinecarboxylic acid ethyl ester, obtained as an oil. The residue was purified further by column chromatography on silica gel (65 g) using a mixture of dichloromethane and methanol (99.2:0.8) as eluent. Rf : 0.20 (SiO2 ; n-heptane/ethyl acetate=1:1 ).

Workup

  1. dry with materialThe organic phase was dried (MgSO4)
  2. customthe solvent evaporated in vacuo
  3. customaffording a residue which
  4. temperaturethe mixture was heated
  5. temperatureat reflux temperature for 16 h
  6. filtrationfiltration
  7. filtrationon filter aid (celite) the solvent
  8. customwas removed by evaporation
  9. dissolutionThe residue was dissolved in diethyl ether (100 ml)
  10. extractionextracted with a 5% tartaric acid solution (3×125 ml)
  11. washThe combined aqueous extracts were washed with diethyl ether and pH
  12. extractionThe neutralised aqueous mixture was extracted with ethyl acetate (4×200 ml)
  13. washThe combined ethyl acetate extracts were washed with water, brine
  14. dry with materialdried (MgSO4)
  15. customThe solvent was evaporated in vacuo
  16. customaffording 2.6 g (32%) of 1-(4-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-1-butyl

Sources & evidence

ORD record
ord-630626c633df4bac9a6acce35aa8cfb4
Source dataset
uspto-grants-1998_04
Patent number
US05741791

Reaction notes

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