反应详情

温度

23 °C

To a suspension of NaH (0.238 g, 5.95 mmol, 1.3 eq, 60%) in THF at 0° C. was added a solution of 4-Bromo-5-methoxy-1H-pyrrolo[2,3-c]pyridine (1.05 g, 4.62 mmol) in THF and the solution stirred until no effervescence was observed (approx. 5 minutes). To the reaction mixture was added (2-Chloromethoxy-ethyl)-trimethyl-silane (1.00 mL, 5.64 mmol, 1.2 eq) and the solution was warmed to 23° C. and stirred for 16 hr. The reaction was quenched using sat'd NaHCO3 (aq) and most of the THF removed under reduced pressure. The aqueous layer was partitioned between EtOAc (100 mL), the organic layer washed with water, brine, dried, and concentrated. The crude reaction was purified using chromatography eluting with 20% EtOAc/Heptane giving 4-Bromo-5-methoxy-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-c]pyridine beige crystalline product (0.950 g, 2.53 mmol, 55%). MS ESI m/z 359.2 (M+2H)+. 1NMR (400 MHz, CDCl3) δ 8.46 (d, J=0.6 Hz 1H), 8.36 (s, 1H), 7.39 (d, J=3.2 Hz, 1H), 6.54 (dd, J=3.2 Hz, 0.6 Hz, 1H), 5.51 (s, 2H), 4.14 (s, 3H), 3.51 (m, 2H), 0.94 (m, 2H), 0.00 (s, 9H).

1. custom(approx. 5 minutes)
2. stirringstirred for 16 hr
3. customThe reaction was quenched
4. custommost of the THF removed under reduced pressure
5. customThe aqueous layer was partitioned between EtOAc (100 mL)
6. washthe organic layer washed with water, brine
7. customdried
8. concentrationconcentrated
9. customThe crude reaction
10. customwas purified
11. washeluting with 20% EtOAc/Heptane