Potassium Carbonate → Ethyl nipecotate

The above alcohol (5.4 g, 0.02 mol) was dissolved in toluene (160 ml) and triethylamine (7 ml) was added. Methanesulfonyl chloride (2.5 ml, 0.032 mol) was added dropwise and when addition was complete the reaction mixture was stirred for 2 h. Water was added and the phases were separated. 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).

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

ORD record

ord-54b468bab79e472abbd69e68bcea2597

Source dataset

uspto-grants-1998_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05795888