反应详情

温度

-50 °C

n-BuLi (15% strength solution in n-hexane, 45 ml, 104 mmol) was added dropwise to a solution, cooled to −85° C., of diisopropylamine (15 ml, 106 mmol) in abs. THF (150 ml) in a double-necked flask which had been dried by heating and flushed with argon: temperature increase to −50° C. After the addition had ended, the light-yellow solution was stirred at −85° C for 55 min. At −85° C., a solution of 2-chloro-4-methylpyridine (2-chloro-γ-picoline, 8.6 g; 68 mmol) in abs. THF (75 ml) was added dropwise to this initial charge: temperature increase to −50° C., initial change of color to purple. After the addition had ended, the reaction mixture was stirred at −85° C. for 1 h, and a solution of 20 (12.4 g; 68 mmol) in abs. THF (75 ml) was added at this temperature over a period of 3 min: temperature increase to −60° C. The purple slurry of the reaction mixture was stirred at −85° C. for 1 h and then, over a period of 1 h, warmed to 0° C. The mixture was poured into saturated NaCl solution (300 ml) which had been covered with ethyl acetate (300 ml). The organic phase was removed and the aqueous phase was extracted with ethyl acetate (2×250 ml) and a little brown foamy precipitate of 1,3-bis-(2-chloropyridin-4-yl)-2-(4-fluorophenyl)propan-2-ol separated off at the interface. The combined organic extract was washed with saturated NaCl solution, dried over NaSO4 and concentrated. The oily residue was taken up in a little tert-butyl methyl ether and stored at 4° C. overnight. The crystals were filtered off and dried.

1. dry with materialTHF (150 ml) in a double-necked flask which had been dried
2. temperatureby heating
3. customflushed with argon
4. additionAfter the addition
5. customAt −85° C.
6. additionthis initial charge
7. temperaturetemperature increase to −50° C.
8. additionAfter the addition
9. stirringthe reaction mixture was stirred at −85° C. for 1 h
10. temperaturetemperature increase to −60° C
11. stirringThe purple slurry of the reaction mixture was stirred at −85° C. for 1 h
12. waitover a period of 1 h
13. temperaturewarmed to 0° C
14. customThe organic phase was removed
15. extractionthe aqueous phase was extracted with ethyl acetate (2×250 ml)
16. customa little brown foamy precipitate of 1,3-bis-(2-chloropyridin-4-yl)-2-(4-fluorophenyl)propan-2-ol separated off at the interface
17. extractionThe combined organic extract
18. washwas washed with saturated NaCl solution
19. dry with materialdried over NaSO4
20. concentrationconcentrated
21. waitstored at 4° C. overnight
22. filtrationThe crystals were filtered off
23. customdried