Triethylsilane → Ethyl 5-bromo-3-(4-thiepanyl)-1H-indole-7-carboxylate

Temperature

0 °C

To a solution of 4-thiepanone (900 mg, 6.9 mmol, 1.1 eq) in dry dichloromethane (30 mL) was added activated molecular sieves (4 Å, beads, spatula tip full) and the solution was cooled to 0° C. using an ice water bath. Trimethylsilyl trifluoromethanesulfonate (1.25 mL, 6.9 mmol, 1.1 eq) was added dropwise to the ketone solution, followed by the dropwise addition of ethyl 5-bromo-1H-indole-7-carboxylate (1.69 g, 6.3 mmol, 1 eq) as a solution in dichloromethane (10 mL). The reaction mixture was stirred at rt for 2 h, then warmed to 35° C. for 45 minutes. The deep red reaction mixture was cooled to 0° C. and triethylsilane (2 mL, 12.6 mmol, 2 eq) was added. The mixture was warmed to rt for 30 minutes, then was quenched by the addition of saturated aq. sodium bicarbonate. The aqueous layer was extracted with dichloromethane (2×50 mL), and the combined organic extracts were dried over sodium sulfate, filtered through a thin pad of silica gel (to remove baseline impurities), eluting with 50% ethyl acetate in hexanes, and concentrated to afford the crude product as a yellow residue. The crude material was purified by Isco Combiflash, eluting with 0-30% ethyl acetate in hexanes (120 gram column). The title compound was obtained as a yellow residue (540 mg, 24%).

1. temperaturewarmed to 35° C. for 45 minutes
2. customThe deep red reaction mixture
3. temperaturewas cooled to 0° C.
4. temperatureThe mixture was warmed to rt for 30 minutes
5. customwas quenched by the addition of saturated aq. sodium bicarbonate
6. extractionThe aqueous layer was extracted with dichloromethane (2×50 mL)
7. dry with materialthe combined organic extracts were dried over sodium sulfate
8. filtrationfiltered through a thin pad of silica gel (to remove baseline impurities)
9. washeluting with 50% ethyl acetate in hexanes
10. concentrationconcentrated
11. customto afford the crude product as a yellow residue
12. customThe crude material was purified by Isco Combiflash
13. washeluting with 0-30% ethyl acetate in hexanes (120 gram column)

ORD record

ord-743c80f197b04aa68e71d19831c0a98c

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08372875B2