反应详情

温度

65 °C

To the crude product solution (1R,4R)-1,4-bis(4-nitrophenyl)butane-1,4-diyl dimethanesulfonate (7.35 g, 13.39 mmol) was added 4-tert-butylaniline (13.4 g, 90 mmol) at 23° C. over 1 minute. The reaction was heated to 65° C. for 2 h. After completion, the reaction mixture was cooled to 23° C. and diluted with 2-methyltetrahydrofuran (100 mL) and 1 M HCl (150 mL). After partitioning the phases, the organic phase was treated with 1 M HCl (140 mL), 2-methyltetrahydrofuran (50 mL), and 25 wt % aq. NaCl (100 mL), and the phases were partitioned. The organic phase was washed with 25 wt % aq. NaCl (50 mL), dried over MgSO4, filtered, and concentrated in vacuo to approximately 20 mL. Heptane (30 mL) and additional 2-methyltetrahydrofuran were added in order to induce crystallization. The slurry was concentrated further, and additional heptane (40 mL) was slowly added and the slurry was filtered, washing with 2-methyltetrahydrofuran:heptane (1:4, 20 mL). The solids were suspended in MeOH (46 mL) for 3 h, filtered, and the wet solid was washed with additional MeOH (18 mL). The solid was dried at 45° C. in a vacuum oven for 16 h to provide (2S,5S)-1-(4-tert-butylphenyl)-2,5-bis(4-nitrophenyl)pyrrolidine (3.08 g, 51% 2-step yield).

1. temperatureAfter completion, the reaction mixture was cooled to 23° C.
2. customAfter partitioning the phases
3. additionthe organic phase was treated with 1 M HCl (140 mL), 2-methyltetrahydrofuran (50 mL), and 25 wt % aq. NaCl (100 mL)
4. customthe phases were partitioned
5. washThe organic phase was washed with 25 wt % aq. NaCl (50 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo to approximately 20 mL
9. additionHeptane (30 mL) and additional 2-methyltetrahydrofuran were added in order
10. customcrystallization
11. concentrationThe slurry was concentrated further
12. additionadditional heptane (40 mL) was slowly added
13. filtrationthe slurry was filtered
14. washwashing with 2-methyltetrahydrofuran:heptane (1:4, 20 mL)
15. filtrationfiltered
16. washthe wet solid was washed with additional MeOH (18 mL)
17. customThe solid was dried at 45° C. in a vacuum oven for 16 h