反应详情

温度

0 °C

General Note: The reaction was run in such a way as to minimize exposure to light. Reactions were run under a layer of foil to block light and the lab lights were turned off while manipulating the reaction mixtures. To a suspension of titanocenedichloride (0.560 g, 2.198 mmol) in toluene (18 mL) at 0° C. was added methyllithium (1.6 M in diethyl ether, 3.4 mL, 5.5 mmol) dropwise. The reaction was stirred at 0° C. for 1 h. The reaction was quenched by addition of 9 mL of a 6% ammonium chloride solution. The heterogeneous mixture was filtered through a course frit and added to the sep funnel. The layers were separated and the organic layer dried over magnesium sulfate. The solution was filtered and treated with (1-(tert-butoxycarbonyl)-4-(4-fluorophenyl)piperidin-4-yl)methyl 6-chloro-2-oxo-1,3-bis((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-benzo[d]imidazole-4-carboxylate (0.560 g, 0.733 mmol) and N-cyclohexyl-N-methylcyclohexanamine (0.078 mL, 0.366 mmol) and the mixture concentrated to ca. ⅓ its volume. The bath temperature was maintained at 30° C. while the reaction mixture was being concentrated. The reaction flask was flushed with a stream of nitrogen and fitted with a reflux condenser and the resulting solution was placed in an oil bath preheated to 80° C. The bath temperature was set to 80° C. and stirred at that temperature for 2 h. The reaction was diluted with ˜20 mL of hexanes to precipitate some of the titanocenes with stirring. To decompose the remaining titanocene, silica gel (excess) was added as a solid with vigorous stirring to the suspension at 0° C. The ice bath was removed and stirring continued for 15 min. The resulting suspension was filtered and the resulting pad washed with 25% ethyl acetate/n-hexane. The mother liquor was concentrated and loaded onto a silica gel column (10% ethyl acetate/n-hexane). After several volumes at 10%, the gradient was ramped to 25% ethyl acetate/n-hexane to give 470 mg (84%) as a very faint yellow solid. 1H-NMR (CD3OD, 500 MHz) δ 7.36 (dd, J=8.9, 5.2 Hz, 2H), 7.19 (d, J=2.1 Hz, 1H), 7.02 (m, 2H), 6.84 (d, J=2.1 Hz, 1H), 5.24 (s, 2H), 4.59 (s, 2H), 4.43 (d, J=2.7 Hz, 1H), 4.22 (d, J=2.5 Hz, 1H), 3.78 (s, 2H), 3.69 (m, 2H), 3.54 (t, J=7.8 Hz, 2H), 3.26 (m, 2H), 2.94 (bs, 2H), 2.19 (m, 2H), 1.78 (m, 2H), 1.36 (s, 9H), 0.85 (t, J=7.9 Hz, 2H), 0.66 (t, J=7.9 Hz, 2H), −0.10 (s, 9H), −0.16 (s, 9H); 13C NMR (126 MHz, CD3OD) δ ppm 163.0 (d, J=245 Hz), 158.7, 156.5 (d, J=14 Hz), 139.4 (d, J=3.8 Hz), 131.8, 130.6 (d, J=7.7 Hz), 128.3, 125.6, 125.1, 124.1, 116.3 (d, J=21 Hz), 110.7, 89.2, 81.1, 77.8, 71.6, 67.4, 66.9, 41.8, 33.2, 28.7, 18.63, 18.58, −1.29, −1.32. Mass spec.: 784.01 (MNa)+.

1. customthe reaction mixtures
2. customThe reaction was quenched by addition of 9 mL of a 6% ammonium chloride solution
3. filtrationThe heterogeneous mixture was filtered through a course frit
4. additionadded to the sep funnel
5. customThe layers were separated
6. dry with materialthe organic layer dried over magnesium sulfate
7. filtrationThe solution was filtered
8. concentrationthe mixture concentrated
9. temperatureThe bath temperature was maintained at 30° C. while the reaction mixture
10. concentrationwas being concentrated
11. customThe reaction flask was flushed with a stream of nitrogen
12. customfitted with a reflux condenser
13. customthe resulting solution was placed in an oil bath
14. custompreheated to 80° C
15. customwas set to 80° C.
16. stirringstirred at that temperature for 2 h
17. additionThe reaction was diluted with ˜20 mL of hexanes
18. customto precipitate some of the titanocenes
19. stirringwith stirring
20. additionwas added as a solid
21. stirringwith vigorous stirring to the suspension at 0° C
22. customThe ice bath was removed
23. stirringstirring
24. waitcontinued for 15 min
25. filtrationThe resulting suspension was filtered
26. washthe resulting pad washed with 25% ethyl acetate/n-hexane
27. concentrationThe mother liquor was concentrated
28. customto give 470 mg (84%) as a very faint yellow solid