Synthesis
The general procedure for synthesizing 1-N-Cbz-2-methylpiperazine from 2-methylpiperazine and benzyl chloroformate is as follows: referring to Example 5, 10.02 g (0.100 mol) of racemic 2-methylpiperazine was added to a 200 mL four-necked flask equipped with a pH meter and a dropping funnel, followed by the addition of 80.2 g of 1 -butanol to solubilize it, and then the addition of 20.1 g of water (water content of 20.0 wt%). Benzyl chloroformate was slowly added dropwise under vigorous stirring. At the same time, the pH of the reaction system was maintained between 7.5 and 8.5 by dropwise addition of 48 wt% aqueous sodium hydroxide. If necessary, an ice bath was used for cooling to maintain the internal temperature at 23 to 26°C (final water content of 23.0 wt%). After completion of the dropwise addition, the reaction was continued under vigorous stirring for 2 hours. A sample of the reaction solution was analyzed and showed a 50.4% yield of 1-benzyloxycarbonyl-2-methylpiperazine.
