反应详情

温度

80 °C

To a 12-L three-neck round bottom flask equipped with a mechanical stirrer, Claisen adapter with a nitrogen inlet and a temperature probe, and a nitrogen outlet was charged with the product of Step B (382 g, 1.26 mol, 1 eq) and CH2Cl2 (6.5 L). N-(phenylseleno)phthalimide (419 g, 1.39 mol, 1.1 eq) was added followed by BF3 etherate (16 mL, 0.126 mol, 0.1 eq) directly added by graduated cylinder. The reaction steadily climbed from 15° C. to 24° C. and within 10 min, the reaction formed a pink precipitate. Ten min later, the reaction became thick with a white precipitate and the temperature began to decrease. The reaction was checked by HPLC and found to be complete. The reaction was filtered through Celite (removing the phthalimide impurity), the filter cake was washed with CH2Cl2 (750 mL) until the filtrate was no longer orange. The filtrate was transferred to a separatory funnel, washed with aqueous NaOH (0.5 M, 2×1350 mL), brine (2×1 L), and the organic layer was dried over Na2SO4. [A second run was conducted with 382 g of the product of Step B, under the same conditions, and was worked up and combined at this point]. With about 3 L organics left, toluene (3 L, ˜4 mL/g starting material) was added and the evaporation continued. Shortly after the toluene addition, crystallization occurred. The 20-L round bottom flask was transferred to a heating mantel, and the contents heated to 80° C., until the solid dissolved. The flask was transferred back to the rotary evaporator, reference material was used to seed the crystallization, and the flask swirled (no heat) until the product started to crystallize. Ice was added to the bath and the contents of the flask swirled at 15° C. (external temp) for 30 min. The product was filtered, washed with ice-cold toluene and air-dried for 1 h, and afforded the product of Step C. 1H NMR (CHLOROFORM-d) δ: 7.49-7.56 (m, 2H), 7.23-7.29 (m, 3H), 5.05 (br. s., 1H), 4.46 (br. s., 1H), 4.29 (s, 1H), 3.86-3.97 (m, 2H), 3.57-3.69 (m, 3H), 1.98-2.08 (m, 1H), 1.86-1.97 (m, 2H), 1.73-1.86 (m, 2H), 1.41 (s, 9H). Calculated for C19H27NO4Se: 436.1 (M+23). found: 436.1.

1. customTo a 12-L three-neck round bottom flask equipped with a mechanical stirrer
2. additiondirectly added by graduated cylinder
3. customThe reaction
4. customthe reaction formed a pink precipitate
5. customTen min
6. filtrationThe reaction was filtered through Celite (
7. customremoving the phthalimide impurity), the filter cake
8. washwas washed with CH2Cl2 (750 mL) until the filtrate
9. customThe filtrate was transferred to a separatory funnel
10. washwashed with aqueous NaOH (0.5 M, 2×1350 mL), brine (2×1 L)
11. dry with materialthe organic layer was dried over Na2SO4
12. additionWith about 3 L organics left, toluene (3 L, ˜4 mL/g starting material) was added
13. customthe evaporation
14. additionShortly after the toluene addition, crystallization
15. dissolutiondissolved
16. customThe flask was transferred back to the rotary evaporator, reference material
17. customthe crystallization
18. temperatureno heat) until the product
19. customto crystallize
20. additionIce was added to the bath
21. customswirled at 15° C.
22. customfor 30 min
23. filtrationThe product was filtered
24. washwashed with ice-cold toluene
25. customair-dried for 1 h