The general procedure for the synthesis of 1-BOC-4-piperidinecarbohydrazide from ethyl N-Boc-4-piperidinecarboxylate is as follows:
Example 4: Synthesis of tert-butyl 4-(hydrazinocarbonyl)piperidine-1-carboxylate
1. 10.0 g (38.9 mmol) of 4-tert-butyl 4-ethylpiperidine-1,4-dicarboxylate was dissolved in 35 mL of ethanol and 3.8 mL (3.90 g, 78 mmol) of hydrazine hydrate was added slowly under stirring conditions.
2. The reaction mixture was heated to reflux with continuous stirring for 9 hours.
3. Upon completion of the reaction, the mixture was cooled to room temperature, 1.9 mL (39 mmol) of hydrazine hydrate was added, and stirring was continued at reflux for 24 hours.
4. At the end of the reaction, the solvent was removed by concentration under reduced pressure and concentrated again by adding 50 mL of ethanol.
5. 150 mL of ether was added to the concentrate and the mixture was sonicated in an ultrasonic bath for 5 minutes.
6. The solid product was collected by filtration and dried to give 9.20 g of white solid in 97% yield.
Product Characterization.
LCMS (Method 6): Rt = 0.95 min, m/z = 244 (M+H)+
1H-NMR (400 MHz, DMSO-d6): δ = 8.99 (s, 1H), 4.17 (br, 2H), 3.95 (br d, 2H), 2.71 (br, 2H), 2.23 (m, 1H), 1.60 (m, 2H), 1.40 (m, 11H).
