Ammonia → tert-Butyl 4-(methylamino)piperidine-1-carboxylate

To tert-butyl 4-oxo-1-piperidinecarboxylate (3.99 g, 20 mmol) was added ethanol (30 ml), and methylamine hydrochloride (2.70 g, 40 mmol), triethylamine (5.6 ml, 40 mmol) and titanium(IV)isopropoxide (11.8 ml, 40 mmol) were added under ice-cooling with stirring, and the mixture was stirred at room temperature for 8 hr. Then, to the reaction mixture was added sodium borohydride (1.14 g, 30 mmol), and the mixture was stirred at room temperature for 15 hr. To the reaction mixture was added 28% aqueous ammonia, and the reaction solution was filtered off through celite. The filtrate was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted with dichloromethane-ethanol=5:1 mixed solvent, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the solution was concentrated under reduced pressure. The obtained oil was purified by silica gel column chromatography (dichloromethane-methanol) to give the title compound (2.46 g, yield 57%) as a pale-yellow oil.

1. additionwere added under ice-
2. temperaturecooling
3. stirringthe mixture was stirred at room temperature for 8 hr
4. stirringthe mixture was stirred at room temperature for 15 hr
5. filtrationthe reaction solution was filtered off through celite
6. concentrationThe filtrate was concentrated under reduced pressure, water
7. additionwas added to the residue
8. extractionthe mixture was extracted with dichloromethane-ethanol=5:1 mixed solvent
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationThe insoluble material was filtered off
11. concentrationthe solution was concentrated under reduced pressure
12. customThe obtained oil was purified by silica gel column chromatography (dichloromethane-methanol)

ORD record

ord-f1c3b462808844cfa24c9ece0a55efcf

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08513235B2