172843-97-9

39124-19-1

24424-99-5

172843-97-9

[Step 2] Synthesis of 4-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-carboxylic acid: to an aqueous solution (30 mL) of 8-oxa-1,3-diazaspiro[4.5]decane-2,4-dione (2.2 g, 13 mmol) was added calcium hydroxide (3.0 g, 41 mmol). The reaction mixture was heated and refluxed under stirring for 48 h. The reaction mixture was subsequently filtered through diatomaceous earth and the filtrate was washed with hot water. The filtrate was concentrated under reduced pressure and the resulting crude product was dissolved in a solvent mixture of water, 1,4-dioxane and methanol (water:1,4-dioxane:methanol = 10:10:3, 23 mL). To this solution was added di-tert-butyl dicarbonate (3.4 g, 16 mmol) and sodium hydroxide (0.50 g, 13 mmol) at room temperature. The reaction mixture was stirred at room temperature for 15 hours and then concentrated under reduced pressure. Dilute hydrochloric acid (15 mL) was added to the concentrated crude product and extracted with a solvent mixture of chloroform and methanol (chloroform:methanol=10:1). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 4-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-carboxylic acid (2.6 g, 82% yield).