Diisopropylamine → 2-Bromo-5-fluoro-4-(triethylsilyl)pyridine

To a solution of diisopropylamine (25.3 g, 250 mmol) in THF (400 ml) was added n-BuLi (100 ml, 2.5 mol/L in hexanes) below −50° C. A solution of 2-bromo-5-fluoropyridine (41.9 g, 238 mmol) in THF (60 ml) was added to the LDA-solution at −78° C. in a dropwise manner below −63° C. After 60 minutes at −78° C. triethylchlorosilane (44 ml, 262 mmol) was added in a fast manner keeping the temperature below −50° C. The cooling bath was removed and the reaction mixture was allowed to reach −20° C. The reaction mixture was poured on a mixture of 1M aq. HCl (250 ml) and aq. NH4Cl (10%). Tert.-butyl methyl ether was added and the layers were separated. The organic phase was washed with brine, dried over magnesium sulfate, filtered and evaporated to give a yellow liquid. Distillation (bp. 99-101° C., 0.5 mm Hg). afforded the title compound as a slightly yellow liquid: 66.26 g (96% yield) 15 1H-NMR (400 MHz, CDCl3): 8.17 (s, 1H), 7.42 (d, 1H), 1.01-0.97 (m, 9H), 0.92-0.87 (m, 6H).

1. customthe temperature below −50° C
2. customThe cooling bath was removed
3. customto reach −20° C
4. additionThe reaction mixture was poured on a mixture of 1M aq. HCl (250 ml) and aq. NH4Cl (10%)
5. additionTert.-butyl methyl ether was added
6. customthe layers were separated
7. washThe organic phase was washed with brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. customevaporated
11. customto give a yellow liquid
12. distillationDistillation (bp. 99-101° C., 0.5 mm Hg)

ORD record

ord-6719701bc1d84da3b0480c568bc814b1

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08865712B2