Methyl Ethyl Ketone → HCID 70203632, compound

A mixture of the above methanesulfonate (2.5 g), (R)-3-piperidinecarboxylic acid ethyl ester tartrate (4.6 g, 15.1 mmol), dry potassium carbonate (6,3 g, 45.4 mmol), and methyl ethyl ketone (100 ml) was heated at reflux temperature for 48 hours under an atmosphere of nitrogen. The cooled reaction mixture was quenched with water (100 ml) and extracted with diethyl ether (100 ml). The organic extract was washed with saturated brine (80 ml), dried (Na2SO4), filtered and the solvent evaporated in vacuo. The crude product (3.1 g) was purified by column chromatography on silica gel (600 ml) using a mixture of ethyl acetate/heptane (1:2) as eluent. This afforded 1.9 g of crude (R)-1-(3-(11,12-dihydro-dibenz[a,e]cycloocten-5-yl)-1 -propyl)-3-piperidinecarboxylic acid ethyl ester. The ethyl ester was suspended in water (150 ml) and concentrated hydrochloric acid was added to pH=1. The aqueous phase was washed with diethyl ether (100 ml) basified to pH=8 with 20% sodium hydroxide and extracted with diethyl ether (2×100 ml). The combined organic extracts were washed with brine (80 ml), dried (MgSO4), filtered and the solvent was evaporated in vacuo affording 1.1 g (36%) of (R)-1-(3-(11,12-dihydro-dibenz[a,e]cycloocten-5-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil.

1. temperaturewas heated
2. temperatureat reflux temperature for 48 hours under an atmosphere of nitrogen
3. customThe cooled reaction mixture
4. customwas quenched with water (100 ml)
5. extractionextracted with diethyl ether (100 ml)
6. extractionThe organic extract
7. washwas washed with saturated brine (80 ml)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customthe solvent evaporated in vacuo
11. customThe crude product (3.1 g) was purified by column chromatography on silica gel (600 ml)
12. additiona mixture of ethyl acetate/heptane (1:2) as eluent
13. additionconcentrated hydrochloric acid was added to pH=1
14. washThe aqueous phase was washed with diethyl ether (100 ml)
15. extractionextracted with diethyl ether (2×100 ml)
16. washThe combined organic extracts were washed with brine (80 ml)
17. dry with materialdried (MgSO4)
18. filtrationfiltered
19. customthe solvent was evaporated in vacuo

ORD record

ord-58427d7359224d5f9815e6b466906a6d

Source dataset

uspto-grants-1997_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05698551