Nitrogen → 4-(Tert-butyldimethylsilyl)-2,3,5-trifluoropyridine

Temperature

-78 °C

n-BuLi (41.09 mL of 1.6 M, 65.75 mmol) was added dropwise to a solution of diisopropylamine (6.919 g, 9.583 mL, 68.38 mmol) in THF (130 mL), cooled to −5° C. (under N2). After stirring for 15 min, the reaction mixture was cooled down to −78° C. 2,3,5-Trifluoropyridine (7 g, 52.60 mmol) was added dropwise to the reaction mixture which was stirred for 45 min. A solution of tert-butyl-chloro-dimethyl-silane (10.31 g, 68.38 mmol) in THF (15 mL) was added to the reaction mixture. The reaction mixture was stirred at −78° C. for 2 hours. It was quenched with a saturated ammonium chloride aqueous solution (˜50 ml). The reaction mixture was partitioned between ethyl acetate and a saturated sodium bicarbonate aqueous solution. The aqueous was extracted with ethyl acetate twice. The combined organics were washed with brine. The organic was dried over magnesium sulfate and concentrated in vacuo after filtration. The crude mixture was purified on silica gel, eluting with petrol ether/ethyl acetate 0 to 20% to afford the title compound as a pale yellow solid (11.8 g, 90%). 1H NMR (CDCl3) 0.34 (6H, s), 0.87 (9H, s), 7.71 (1H, s).

1. stirringwas stirred for 45 min
2. stirringThe reaction mixture was stirred at −78° C. for 2 hours
3. customIt was quenched with a saturated ammonium chloride aqueous solution (˜50 ml)
4. customThe reaction mixture was partitioned between ethyl acetate
5. extractionThe aqueous was extracted with ethyl acetate twice
6. washThe combined organics were washed with brine
7. dry with materialThe organic was dried over magnesium sulfate
8. concentrationconcentrated in vacuo
9. filtrationafter filtration
10. customThe crude mixture was purified on silica gel
11. washeluting with petrol ether/ethyl acetate 0 to 20%

ORD record

ord-cdfec26986cf4168b52b4e9d97a7ee0a

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569337B2