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

Participants

Reaction Conditions

Reaction Steps

(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.

Provenance & Evidence