Triethylsilane → ethyl 5-bromo-3-(8-thiabicyclo[3.2.1]oct-3-yl)-1H-indole-7-carboxylate

Temperature

23 °C

To a solution of 8-thiabicyclo[3.2.1]octan-3-one (1.33 g, 9.32 mmol, 1 eq) in dry dichloromethane (50 mL) was added a spatula tip full of activated 4 A molecular sieves (beads). The ketone solution was cooled to 0° C., and trimethylsilyl triflate (1.7 mL, 9.41 mmol, 1 eq) was added dropwise followed by a solution of ethyl 5-bromo-1H-indole-7-carboxylate (2.5 g, 9.32 mmol, 1 eq) in dichloromethane (25 mL). The mixture was stirred at 23° C. overnight, then was cooled to 23° C. and triethylsilane (2.3 mL, 14.4 mmol, 1.5 eq) was added in a single portion. The reaction was stirred at 23° C. for 1.5 h, then quenched by the addition of saturated aqueous sodium bicarbonate. The mixture was extracted with dichloromethane, and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by Isco Combiflash, 120 gram column, eluting with 0-30% ethyl acetate in hexanes. The ethyl 5-bromo-3-(8-thiabicyclo[3.2.1]oct-3-yl)-1H-indole-7-carboxylate was obtained as a mixture of isomers (2.38 g, 65%).

1. temperaturewas cooled to 23° C.
2. stirringThe reaction was stirred at 23° C. for 1.5 h
3. customquenched by the addition of saturated aqueous sodium bicarbonate
4. extractionThe mixture was extracted with dichloromethane
5. dry with materialthe combined organic extracts were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by Isco Combiflash, 120 gram column
9. washeluting with 0-30% ethyl acetate in hexanes

ORD record

ord-3b9ee0ca21eb40fdbcbe18705a79944d

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071584B2