Benzyl Alcohol → rel-1-(tert-butyl) 3-methyl (3R,5S)-5-aminopiperidine-1,3-dicarboxylate

Temperature

100 °C

(3S,5R)-1-(tert-Butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid (2.83 g) was suspended in toluene (36 ml), diphenylphosphoryl azide (2.60 ml) and triethylamine (1.70 ml) were added and the mixture was stirred at 100° C. for 1 hr. The reaction mixture was cooled to room temperature, benzyl alcohol (1.53 ml) and triethylamine (7.00 ml) were added and the mixture was stirred at 80° C. for 3 hr. The reaction mixture was concentrated, and the residue was dissolved in ethyl acetate. The mixture was washed with water, 0.5 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine in this order, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography. The fraction eluted with ethyl acetate-hexane (1:3-3:1) was concentrated under reduced pressure. The obtained residue was dissolved in methanol (60 ml), 10% palladium-carbon (50% containing water) (150 mg) was added, and the mixture was subjected to catalytic reduction at ambient temperature under a hydron atmosphere (1 atm) for 5 hr. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure to give the object compound (1.83 g) as an oil.

1. temperatureThe reaction mixture was cooled to room temperature
2. stirringthe mixture was stirred at 80° C. for 3 hr
3. concentrationThe reaction mixture was concentrated
4. dissolutionthe residue was dissolved in ethyl acetate
5. washThe mixture was washed with water, 0.5 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine in this order
6. dry with materialdried over anhydrous magnesium sulfate
7. customThe solvent was evaporated under reduced pressure
8. customthe residue was purified by silica gel column chromatography
9. washThe fraction eluted with ethyl acetate-hexane (1:3-3:1)
10. concentrationwas concentrated under reduced pressure
11. dissolutionThe obtained residue was dissolved in methanol (60 ml)
12. addition10% palladium-carbon (50% containing water) (150 mg) was added
13. customwas subjected to catalytic reduction at ambient temperature under a hydron atmosphere
14. customfor 5 hr
15. filtrationThe catalyst was filtered off
16. concentrationthe filtrate was concentrated under reduced pressure

ORD record

ord-0a2362031b9448bcabd39700417bd0f1

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329691B2