1,2-Dibromoethane → Methyl 5-bromo-3-(2,2,2-trifluoroacetamido)thiophene-2-carboxylate

Temperature

-78 °C

To a solution of diisopropylamine (20 mL) in tetrahydrofuran (200 mL) was added 1.6M n-butyllithium/hexane solution (82.4 mL) while stirring under ice-cooling, and the mixture was stirred at 0° C. for 15 min. After stirring, the reaction system was cooled to −78° C., and a solution of methyl 3-[(trifluoroacetyl)amino]thiophene-2-carboxylate (10 g) in tetrahydrofuran (50 mL) was added dropwise. After the completion of the dropwise addition, the mixture was stirred at the same temperature for 1 hr, and 1,2-dibromoethane (20.6 mL) was added. After stirring at the same temperature for 30 min, the reaction system was allowed to warm to room temperature, and further stirred for 30 min. The reaction system was poured into saturated aqueous sodium hydrogen carbonate (600 mL), and the mixture was extracted with ethyl acetate, washed with brine, and dried over anhydrous sodium sulfate. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (5.3 g) as a yellow solid.

1. temperaturecooling
2. stirringthe mixture was stirred at 0° C. for 15 min
3. stirringAfter stirring
4. additionAfter the completion of the dropwise addition
5. stirringthe mixture was stirred at the same temperature for 1 hr
6. stirringAfter stirring at the same temperature for 30 min
7. temperatureto warm to room temperature
8. stirringfurther stirred for 30 min
9. extractionthe mixture was extracted with ethyl acetate
10. washwashed with brine
11. dry with materialdried over anhydrous sodium sulfate
12. customInsoluble material was removed by filtration
13. concentrationthe filtrate was concentrated under reduced pressure
14. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

ORD record

ord-a943cabd0a5c4a819c743f6218c4f7ab

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08722660B2