反应详情

1-Cyclobutyl-piperazine di-hydrochloride (D6)(1.8 g) in DMF (15 ml) was stirred with sodium hydrogen carbonate (1.53 g) for 5 min before being added to a DMF (15 ml) solution of 1-tert-butoxycarbonyl-piperidine-4-carboxylic acid (1.94 g), EDCl (3.2 g) and HOAT (0.05 g). After 4 h the reaction was diluted with EtOAc and washed with saturated sodium hydrogen carbonate solution and brine (3×), before being evaporated. The residue was dissolved in a small volume of EtOAc and treated with TFA (90% TFA/water). After 2 h toluene was added and the reaction evaporated and re-evaporated from toluene. The residue was taken up into EtOAc and treated with 2N HCl in diethyl ether. The precipitate was filtered, washed with diethyl ether and dried under vacuum. Crystallisation from ethanol/diethyl ether afforded the title compound (D7)(1.74 g). LCMS electrospray (+ve) 252(MH+).

1. washwashed with saturated sodium hydrogen carbonate solution and brine (3×)
2. custombefore being evaporated
3. dissolutionThe residue was dissolved in a small volume of EtOAc
4. additiontreated with TFA (90% TFA/water)
5. additionAfter 2 h toluene was added
6. customthe reaction evaporated
7. customre-evaporated from toluene
8. additiontreated with 2N HCl in diethyl ether
9. filtrationThe precipitate was filtered
10. washwashed with diethyl ether
11. customdried under vacuum
12. customCrystallisation from ethanol/diethyl ether