反应详情

温度

40 °C

1,4-Bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid (1.0 g, 3.03 mmol) was suspended in THF (5 mL) and pyridine (0.36 mL), DMF (0.1 mL) was added, followed by thionyl chloride (0.23 mL, 3.03 mmol). The reaction mixture was stirred at 40° C. for 4 h and then concentrated under reduced pressure. The crude product was dissolved in CH2Cl2 and transferred to a sealed tube. A saturated solution of ammonia in dioxane (10 mL) was added to the compound and the resulting reaction mixture was stirred at 40° C. for 2 h followed by room temperature stirring for 12 h. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in 1.5 N HCl. The aqueous layer was washed with diethyl ether and then basified with 1N sodium hydroxide solution. The organic product was extracted with CH2Cl2. The combined extracts were dried over anhydrous sodium sulfate, and concentrated under reduced pressure to get tert-butyl 3-carbamoylpiperazine-1-carboxylate (340 mg, yield 49%), which was carried through without further purification. 1H NMR (400 MHz, CDCl3) δ 6.70 (br s, 1H), 5.51 (br s, 1H), 4.06-4.03 (m, 1H), 3.77 (m, 1H), 3.37-3.33 (m, 1H), 3.11-2.95 (m, 3H), 2.81-2.76 (m, 1H), 1.47 (s, 9H).

1. concentrationconcentrated under reduced pressure
2. dissolutionThe crude product was dissolved in CH2Cl2
3. customtransferred to a sealed tube
4. additionA saturated solution of ammonia in dioxane (10 mL) was added to the compound
5. customthe resulting reaction mixture
6. stirringwas stirred at 40° C. for 2 h
7. customfollowed by room temperature
8. stirringstirring for 12 h
9. concentrationThe reaction mixture was concentrated under reduced pressure
10. dissolutionthe residue was dissolved in 1.5 N HCl
11. washThe aqueous layer was washed with diethyl ether
12. extractionThe organic product was extracted with CH2Cl2
13. dry with materialThe combined extracts were dried over anhydrous sodium sulfate
14. concentrationconcentrated under reduced pressure