Dimethoxymethane → 1-(6-Bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-3-methoxy-propan-1-one

Temperature

0 °C

To a solution of 1-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-ethanone (11.6 g, 33.9 mmol, example 1, step b) in dichloromethane (50 ml) was added Hünigs-base (6.21 ml, 35.6 mmol) at 0° C. followed by TMS-triflate (6.43 ml, 35.52 mmol, 1.05 eq.) under nitrogen. The reaction mixture was stirred at 0° C. for 40 minutes. Dimethoxymethane (2.71 g, 35.6 mmol) and 2,6-di-tert-butylpyridine (0.648 g, 3.39 mmol) was added drop wise at 0° C. TMS-triflate (0.61 ml, 3.39 mmol) was then added to the reaction mixture. After 30 min the cooling bath was removed and stirring was continued at rt over night (18 h). The reaction mixture was poured onto cold brine, diluted with ethyl acetate and the organic phase was washed thoroughly with 10% NaHSO4 solution, sat. sodium bicarbonate solution (saturated with NaCl) and brine, dried over sodium sulfate, filtered and evaporated. The crude product (13.52 g) was chromatographed over silica gel (320 g, cyclohexane/ethyl acetate 95:5) to give the title compound as a yellow liquid: 9.18 g (72% yield).

1. customAfter 30 min the cooling bath was removed
2. stirringstirring
3. waitwas continued at rt over night
4. custom(18 h)
5. additionThe reaction mixture was poured onto cold brine
6. additiondiluted with ethyl acetate
7. washthe organic phase was washed thoroughly with 10% NaHSO4 solution, sat. sodium bicarbonate solution (saturated with NaCl) and brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. customevaporated
11. customThe crude product (13.52 g) was chromatographed over silica gel (320 g, cyclohexane/ethyl acetate 95:5)

ORD record

ord-2598b699c32b4aaaaa31a1676fbc7a7e

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09163011B2