Hydrochloric Acid → 1-(6-Bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-ethanone

Participants

Reaction Steps

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).

Provenance & Evidence