反应详情

温度

-70 °C

A mixture of N-(1-methylethyl)-2-propanamine (16.7 g) in THF (600ml) was stirred at −70° C. under N2 flow. Butyllithium in hexane (63 ml; 2.5 M) was added portionwise and the temperature was allowed to rise to −40° C. and stirring was continued for 15 minutes. The mixture was cooled to −70° C. and a suspension of 1-(phenylmethyl)benzimidazole (31.3 g) in THF was added dropwise. After stirring for 1 hour at −70° C., 4-(ethoxy-carbonyl)-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (42.5 g) was added dropwise and stirring at −70° C. was continued for 1.5 hours. The temperature was allowed to rise to RT and the mixture was decomposed with water, and further extracted with CH2Cl2. The organic layer was separated, dried, filtered and the solvent evaporated. The residue was crystallized from acetonitrile, yielding 54 g (85.8%) of (1,1-dimethylethyl) 4-[[1-(phenylmethyl)-1H-benzimidazol-2-yl]carbonyl]-1-piperidinecarboxylate (interm. 1; mp. 121.5° C.).

1. customto rise to −40° C.
2. stirringstirring
3. temperatureThe mixture was cooled to −70° C.
4. additionwas added dropwise
5. stirringAfter stirring for 1 hour at −70° C.
6. stirringstirring at −70° C.
7. waitwas continued for 1.5 hours
8. customto rise to RT
9. extractionfurther extracted with CH2Cl2
10. customThe organic layer was separated
11. customdried
12. filtrationfiltered
13. customthe solvent evaporated
14. customThe residue was crystallized from acetonitrile