4-(Trimethylsilyl)-3-butyn-2-one → 2-(5-Fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol

Temperature

-78 °C

To a stirred solution of 2-bromo-5-fluoropyridine (1.76 g, 10.00 mmol) in ether (20 mL) maintained under nitrogen at −78° C. was added a solution of s-butyllithium (1.3M in hexane, 10 mL, 13.00 mmol) dropwise. The reaction mixture was then stirred at −78° C. for 1 hr and 4-(trimethylsilyl)but-3-yn-2-one (1.54 g, 10.98 mmol) was added to the reaction mixture dropwise with stirring at −78° C. The resulting solution was stirred at −78° C. for 2 hr and then quenched by the addition of saturated ammonium chloride solution (5 mL) and water (10 mL). The resulting solution was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified on a silica gel column with ethyl acetate/petroleum ether (1:3) to give 1 g (42%) of the title compound as a yellow oil: LC-MS: m/z=+238 (M+H)+.

1. stirringwith stirring at −78° C
2. stirringThe resulting solution was stirred at −78° C. for 2 hr
3. customquenched by the addition of saturated ammonium chloride solution (5 mL) and water (10 mL)
4. extractionThe resulting solution was extracted with ethyl acetate (3×20 mL)
5. dry with materialThe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude residue was purified on a silica gel column with ethyl acetate/petroleum ether (1:3)

ORD record

ord-a8a94d8aabdb4a79a7bc7b5485874d47

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901313B2