Hydrochloric Acid → Ethyl 3-methylpiperidine-3-carboxylate

Temperature

40 °C

Ethyl-5-chloro-2-cyano-2-methylpentanoate (DE 31 39 301 A1) (10.43 g, 51.2 mmol), PtO2 hydrate (1.16 g) and concentrated HCl (12.5 ml) in absolute EtOH (125 ml) were stirred and heated at 40° C. under hydrogen at normal pressure for 2 h. The cooled solution was filtered. After evaporation of the solvent, the residue was dissolved in absolute EtOH (125 ml). The solution was cooled with an ice-water bath and triethylamine (9.8 g, 96.8 mmol) was added. After the addition the mixture was stirred at RT for 16 h under nitrogen atmosphere. The solvent and triethylamine were evaporated, and the residue was dissolved in DCM (100 ml) and extracted with 1 M HCl (3×100 ml). After separating the layers, ice (150 g) and 5 M NaOH (100 ml) were added to the aqueous layer, which was then extracted with DCM (3×60 ml). The combined extracts were dried, filtered and evaporated to dryness followed by vacuum distillation (bp. 62-65° C./2 mbar) to give 6.0 g of the title compound as a colorless liquid.

1. filtrationThe cooled solution was filtered
2. customAfter evaporation of the solvent
3. dissolutionthe residue was dissolved in absolute EtOH (125 ml)
4. temperatureThe solution was cooled with an ice-water bath
5. additionAfter the addition the mixture
6. customThe solvent and triethylamine were evaporated
7. dissolutionthe residue was dissolved in DCM (100 ml)
8. extractionextracted with 1 M HCl (3×100 ml)
9. customAfter separating the layers, ice (150 g) and 5 M NaOH (100 ml)
10. additionwere added to the aqueous layer, which
11. extractionwas then extracted with DCM (3×60 ml)
12. customThe combined extracts were dried
13. filtrationfiltered
14. customevaporated to dryness
15. distillationfollowed by vacuum distillation (bp. 62-65° C./2 mbar)

ORD record

ord-cc9ecee67500447ba9ff7a9a50bf0697

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08492549B2