Thiophene → 2-Methyl-1-(thiophen-2-yl)propan-1-one

Temperature

0 °C

Aluminum chloride (4.75 g, 35.7 mmol, 3 eq) was diluted in ice cold dichloromethane (30 mL). Isobutyryl chloride (4 mL, 38 mmol, 3.2 eq) in dichloromethane (30 mL) was added to the aluminum chloride suspension at 0° C., and the mixture was stirred at 0° C. for 30 minutes. Thiophene (1 g, 11.9 mmol) was added as a solution in dichloromethane (30 mL) over 10 minutes. The reaction was stirred at 0° C. for 30 minutes, then at rt for 1 h. Bromine (0.65 mL, 12.6 mmol, 1.1 eq) was added dropwise at 0° C., and the reaction mixture was slowly warmed to rt overnight. The mixture was cooled to 0° C., and was carefully quenched by the dropwise addition of water. The reaction mixture was extracted with dichloromethane, and the combined organics washed with saturated aqueous sodium bicarbonate. The combined organics were then dried over sodium sulfate, filtered, and concentrated. The crude product was purified by isco combiflash, eluting with 0-10% ethyl acetate in hexanes to afford a slightly yellow oil (2.3 g, >100%).

1. stirringThe reaction was stirred at 0° C. for 30 minutes
2. waitat rt for 1 h
3. temperaturethe reaction mixture was slowly warmed to rt overnight
4. temperatureThe mixture was cooled to 0° C.
5. customwas carefully quenched by the dropwise addition of water
6. extractionThe reaction mixture was extracted with dichloromethane
7. washthe combined organics washed with saturated aqueous sodium bicarbonate
8. dry with materialThe combined organics were then dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified by isco combiflash
12. washeluting with 0-10% ethyl acetate in hexanes

ORD record

ord-f5370404f99849599cb90e4fd5e6b28a

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071584B2