反应详情

温度

-65 °C

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(4-fluorophenyl)pyrrolidine (0.52 g, 0.87 mmol) and tetrahydrofuran (20 mL). Cool to about −65° C. using a dry-ice/acetone bath. Add dropwise a solution of potassium bis(trimethylsilyl)amide in toluene (2.1 mL, 0.5 M, 1.05 mmol) at such a rate that the temperature of the reaction mixture does not rise above about 60° C. After 1.5 hours, add a solution of 2-picolyl chloride (prepared as described in Example 37.2) (0.13 g, 1.05 mmol) in tetrahydrofuran (5 mL). When the addition of 2-picolyl chloride is complete, warm the reaction mixture to ambient temperature. After 18 hours, dilute the reaction mixture with ethyl acetate, extract twice with a saturated aqueous sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with methanol/ethyl acetate 1/1. Evaporate the product containing fractions to give a residue, dissolve the residue in dichloromethane, filter through a fine filter, and evaporate the filtrate in vacuo to give the title compound.

1. customdoes not rise above about 60° C
2. temperaturewarm the reaction mixture to ambient temperature
3. waitAfter 18 hours
4. extractionextract twice with a saturated aqueous sodium bicarbonate solution
5. dry with materialDry the organic layer over Na2SO4
6. filtrationfilter
7. concentrationconcentrate in vacuo
8. customto obtain a residue
9. customEvaporate the product
10. additioncontaining fractions
11. customto give a residue
12. filtrationfilter through a fine filter
13. customevaporate the filtrate in vacuo