反应详情

To a solution of diisopropylamine (25.4 g, 251 mmol) in THF (500 ml) was added n-BuLi (100 ml, 2.5 mol/L in hexanes) below −50° C. A solution of 2-bromo-5-fluoro-4-triethylsilanyl-pyridine (56.04 g, 193 mmol) in THF (60 ml) was added to the LDA-solution at −78° C. in a dropwise manner below −65° C. After 70 minutes at −78° C. DMA (23.51 ml, 251 mmol) was added dropwise in a fast manner to the deep red solution keeping the temperature below −57° C. After 15 minutes the cooling bath was removed and the reaction mixture was allowed to reach −40° C. The cold reaction mixture was poured on a mixture of 2M aq. HCl (250 ml)/water (200 ml)/brine (100 ml). Tert.-butyl methyl ether was added and the layers were separated. The organic phase was washed twice with brine, dried over magnesium sulfate, filtered and evaporated to give a yellow oil. The crude product (64.76 g) was chromatographed over silica gel (hexane/TBME) to give the title compound as a yellow liquid: 58.3 g (91% yield).

1. customthe temperature below −57° C
2. customAfter 15 minutes the cooling bath was removed
3. customto reach −40° C
4. customThe cold reaction mixture
5. customthe layers were separated
6. washThe organic phase was washed twice with brine
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. customevaporated
10. customto give a yellow oil
11. customThe crude product (64.76 g) was chromatographed over silica gel (hexane/TBME)