Synthesis
The general procedure for the synthesis of tert-butyl (R)-3-carbamoylpiperidine-1-carboxylate from 3-piperidinecarboxamide and di-tert-butyl dicarbonate was as follows: to the reaction mixture obtained in Example 4 was added tetrahydrofuran (THF, 40 mL), followed by the addition of di-tert-butyl dicarbonate (37.2 g, 2.3 eq.). The pH of the reaction mixture was adjusted to 10.0 using sodium hydroxide (NaOH). the reaction mixture was stirred at room temperature for 1 hr, after which the precipitated crystals were collected by filtration to afford (R)-1 -(tert-butoxycarbonyl)piperidinamide as white crystals (15.6 g, yield: 93%). The crystals were analyzed using the method described in Example 3; the results showed an optical purity of 99.8% ee. 1H NMR (400 MHz, CDCl3) data were as follows: δ 5.36 (brs, 2H), 3.94-3.08 (m, 5H), 1.96-1.36 (m, 13H).
