反应详情

温度

-78 °C

To a solution of 3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-6-(2,6-difluorobenzyl)-2-(2,4-difluorophenyl)pyridine (from Step D above, 4.63 g) in THF was added lithium bis(trimethylsilyl)amide (22.0 mL, 1.0 M in THF) at −78° C. After stirring ½ h at −78° C., ethyl 3-(trimethylsilyl)prop-2-ynoate (2.2 mL) was added. The mixture was warmed to 0° C. and stirred for a couple of hours until reaction complete. The reaction was quenched with 0.1 N HCl, and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and concentrated. The residue in THF was added TBAF (25 mL, 1N in THF) at 0° C. and stirred for 1 h. The solution was washed with water, brine, dried over MgSO4 and concentrated. The residue was purified by silica gel (100% methylene chloride) to give title compound (1.08 g).

1. temperatureThe mixture was warmed to 0° C.
2. stirringstirred for a couple of hours until reaction complete
3. customThe reaction was quenched with 0.1 N HCl
4. extractionextracted with ethyl acetate
5. washThe organic layer was washed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. additionThe residue in THF was added TBAF (25 mL, 1N in THF) at 0° C.
9. stirringstirred for 1 h
10. washThe solution was washed with water, brine
11. dry with materialdried over MgSO4
12. concentrationconcentrated
13. customThe residue was purified by silica gel (100% methylene chloride)