反应详情

温度

-30 °C

For this substrate General Procedure 4-K was modified in the following manner. Initially the product from Step A was suspended (not a solution) in THF at −78° C., and following addition of the KN(TMS)2 solution, this suspension was allowed to warm to −30° C., during which the suspension became a solution, and was re-cooled to −78° C. Upon re-cooling to −78° C. a precipitate began to form, therefore the reaction flask containing the mixture was partially raised above the cooling bath until the internal temperature rose to −50° C.; then the trisyl azide solution was added. The cooling bath was removed and the mixture allowed to warm to −20° C. whereupon the mixture had become a nearly homogenous solution, and the AcOH was added. Then the mixture was treated as described in the general procedure. 3-Azido-2,4-dioxo-1,5-bis-(cyclopropylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was purified by trituration with hot to room temperature EtOAc, followed by recrystalization from hot to −23° C. CHCl3/EtOAc/EtOH (5:5:1) and isolated as a white solid.

1. customat −78° C.
2. temperaturewas re-cooled to −78° C
3. temperatureUpon re-cooling to −78° C. a precipitate
4. customto form
5. additionthe reaction flask containing the mixture
6. temperaturewas partially raised above the cooling bath until the internal temperature
7. customrose to −50° C.
8. customThe cooling bath was removed
9. temperatureto warm to −20° C. whereupon the mixture
10. additionthe AcOH was added
11. additionThen the mixture was treated
12. custom3-Azido-2,4-dioxo-1,5-bis-(cyclopropylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was purified by trituration with hot to room temperature EtOAc
13. customfollowed by recrystalization from hot to −23° C
14. customCHCl3/EtOAc/EtOH (5:5:1) and isolated as a white solid