反应详情

温度

0 °C

To a solution of 3a-(R)-benzyl-2-methyl-2,3a,4,5,6,7-hexahydro-pyrazolo[4,3-c]pyridin-3-one, L-tartrate (10.81 g, 0.0275 mol) in ethyl acetate (216.2 mL) at about −66° C. was added TEA (8.43 mL, 0.0605 mol). The mixture was stirred for about 1.5 hours. After removal of the precipitated salt by filtration, 3-benzyloxy-2-(2-tert-butoxycarbonylamino-2-methyl-propionylamino)-propionic acid (8.7 g, 0.0229 mol) and TEA (19.15 mL, 0.1374 mol) were added at about −35° C., followed by the dropwise addition of 50% PPAA in ethyl acetate (27.5 mL, 0.0458 mol). The mixture was stirred for about 2 hours at about −20° C. to about −27° C., then 1.5 hours while the temperature was slowly raised to about 0° C. The reaction mixture was poured into water and extracted with IPE, washed with 7% NaCl solution and concentrated in vacuo. The crude oil that was obtained was treated with IPE/hexane (50/50) to allow crystallization. The product was obtained as a white solid (10.3 g, yield 74.3%).

1. customAfter removal of the precipitated salt
2. additionwere added at about −35° C.
3. stirringThe mixture was stirred for about 2 hours at about −20° C. to about −27° C.
4. extractionextracted with IPE
5. washwashed with 7% NaCl solution
6. concentrationconcentrated in vacuo
7. customThe crude oil that was obtained
8. customcrystallization