Acetic Acid → HCID 11065277, compound

Participants

Reaction Steps

To a mixture of rel-(1R,2S)-2-(methoxycarbonyl)cyclobutanecarboxylic acid (1.3 g) and acetone (15 ml) were added triethylamine (1.7 ml) and ethyl chloroformate (1.1 ml) at −10° C., followed by stirring under ice-cooling for 2 hours. To a reaction mixture was added an aqueous solution (3.3 ml) of sodium azide (1.1 g) under ice-cooling, followed by stirring at room temperature for 4 hours. To the reaction mixture were added water and diethyl ether, and the aqueous layer was then extracted with diethyl ether. The organic layer was combined and washed with a 10% aqueous citric acid solution, a saturated sodium bicarbonate solution, water, and saturated brine in this order, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To the residue were added toluene (20 ml) and benzyl alcohol (2.5 ml), followed by stirring at 130° C. for 21 hours. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=5:1→4:1). To the purified product thus obtained was added pyridine (15 ml), and further added anhydrous acetic acid (3.0 ml) under ice-cooling, followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and a saturated sodium bicarbonate solution was added to the residue, followed by stirring. To the reaction mixture were added ethyl acetate and water, and the aqueous layer was separated and extracted with ethyl acetate. The organic layer was combined and washed with a 10% aqueous citric acid solution, a saturated sodium bicarbonate solution, water, and saturated brine in this order, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1→5:1→4:1) to obtain methyl rel-(1R,2S)-2-{[(benzyloxy)carbonyl]amino}cyclobutanecarboxylate (1.1 g).

Provenance & Evidence