反应详情

温度

-5 °C

The N-Boc-D-tert-butylglycine (7.5 g, 32.4 mmol) was converted to a mixed anhydride by adding ethyl chloroformate (3.41 mL, 35.6 mmol), Et3N (6.8 mL, 48.6 mmol) in anhydrous THF (65 mL, 0.5 M) at −5° C. to 0° C. The mixture was stirred at −5° C. for 30 min. The resulting solid was filtered off and additional anhydrous THF was added to wash the precipitate. The resulting reaction solution was then added to a THF solution of 2,5-difluorobenzimido-hydrazide (5.53 g, 32.4 mmol) at −5° C. Then the reaction was gradually warmed to room temperature and stirred for overnight. Once the reaction was complete, the mixture was partitioned between EtOAc and H2O. The organic layer was separated and washed with H2O, brine, then dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure to give the crude product, which was purified on silica gel column (50% EtOAc in Hexanes) to afford (R)-tert-butyl 1-(2-((2,5-difluorophenyl)(imino)methyl)hydrazinyl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (67%). Rf=0.4 (50% EtOAc in Hexanes). LC/MS (uplc): MH+ 385.3, 0.65 min.

1. filtrationThe resulting solid was filtered off
2. additionadditional anhydrous THF was added
3. washto wash the precipitate
4. customThe resulting reaction solution
5. temperatureThen the reaction was gradually warmed to room temperature
6. stirringstirred for overnight
7. customthe mixture was partitioned between EtOAc and H2O
8. customThe organic layer was separated
9. washwashed with H2O, brine
10. dry with materialdried over anhydrous Na2SO4
11. filtrationfiltered
12. customevaporated under reduced pressure
13. customto give the crude product, which
14. customwas purified on silica gel column (50% EtOAc in Hexanes)