反应详情

温度

-50 °C

A 100-L, four-necked, round-bottomed flask was charged with dimethyl 4-(dibenzylamino)benzene-1,2-dicarboxylate in 38 L of THF from the previous step. While cooling with a dry ice-acetone bath (ca. −50° C.), a solution of lithium aluminum hydride (LiAlH4) in THF (1.0 M, 26 L) was added dropwise via an addition funnel keeping the internal temperature<5° C. (ca. 1.5 h addition). The resulting reaction mixture was aged at −12 to 1° C. for 3 h. Additional LiAlH4 (1.2 L) was added via addition funnel and the reaction mixture was allowed to slowly warm to room temperature over 16 h. A solution of aqueous THF (1.03 L of water diluted with 4 L of THF) was then added slowly keeping the internal temperature<15° C. Next, 1.03 L of a 15% NaOH solution were added in one portion followed by the addition of 3.1 L of water in 5 portions. [note, the reaction mixture gets extremely thick during the second water addition step] The reaction mixture was allowed to warm to room temperature, and then filtered through Solka-Floc® with the aid of 40 L of THF [note, the filtration is slow, ca. 5 h] and concentrated to ca. 21 L (ca. 3 volumes). Toluene (56 L, 8 volumes) was added and the solution was concentrated to ca. 35 L (ca. 5 volumes). Seed crystals were then added to initiate crystallization and the reaction mixture was further concentrated to ca. 28 L (4 volumes). Heptane (70 L) was then added over 90 min and the crystallization was aged at room temperature until <3% of the diol remained in the mother liquor (ca. 3 h). The crystals were collected by filtration, washed with 20 L of a 1:2 toluene:heptane solution and 30 L of heptane, and dried under vacuum with a nitrogen sweep to give the title compound.

1. additionthe internal temperature<5° C. (ca. 1.5 h addition)
2. customThe resulting reaction mixture
3. temperatureto slowly warm to room temperature over 16 h
4. customthe internal temperature<15° C
5. temperatureto warm to room temperature
6. filtrationfiltered through Solka-Floc® with the aid of 40 L of THF [note
7. filtrationthe filtration
8. waitis slow, ca. 5 h
9. concentration] and concentrated to ca. 21 L (ca. 3 volumes)
10. additionToluene (56 L, 8 volumes) was added
11. concentrationthe solution was concentrated to ca. 35 L (ca. 5 volumes)
12. additionSeed crystals were then added
13. customcrystallization
14. concentrationthe reaction mixture was further concentrated to ca. 28 L (4 volumes)
15. additionHeptane (70 L) was then added over 90 min
16. customthe crystallization
17. customwas aged at room temperature until <3% of the diol
18. customremained in the mother liquor (ca. 3 h)
19. filtrationThe crystals were collected by filtration
20. washwashed with 20 L of a 1:2 toluene
21. dry with materialheptane solution and 30 L of heptane, and dried under vacuum with a nitrogen sweep