Diisopropylamine → HCID 86707392, compound

Temperature

0 °C

To a solution of N,N-diisopropylamine (680 μL, 5.19 mmol) in tetrahydrofuran (5 ml) was added dropwise a solution of 1.67 mol/L n-butyllithium in hexane (3.11 ml, 5.19 mmol) at −78° C. under argon atmosphere, and the mixture was stirred at the same temperature for 15 minutes. The reaction solution was slowly warmed to 0° C., and stirred for 20 minutes, and then cooled to −40° C. Then, thereto was added dropwise a solution of 3-bromo-2-(trifluoromethyl)thiophene (1000 mg, 4.33 mmol) in tetrahydrofuran (15 ml). The mixture was stirred at the same temperature for 20 minutes, and the reaction solution was slowly warmed to −10° C., and then stirred for 5 minutes. The reaction solution was cooled to −40° C., and then thereto was added dropwise N,N-dimethylformamide (1 mL). Then, the mixture was slowly warmed to 0° C., and stirred overnight. To the reaction solution was added water, and the mixture was extracted with ethyl acetate twice. The organic layer was combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0→9:1) to give 4-bromo-5-(trifluoromethyl)thiophene-2-carbaldehyde (527 mg, 47%) as a yellow oil.

1. stirringstirred for 20 minutes
2. temperaturecooled to −40° C
3. stirringThe mixture was stirred at the same temperature for 20 minutes
4. temperaturethe reaction solution was slowly warmed to −10° C.
5. stirringstirred for 5 minutes
6. temperatureThe reaction solution was cooled to −40° C.
7. temperatureThen, the mixture was slowly warmed to 0° C.
8. stirringstirred overnight
9. extractionthe mixture was extracted with ethyl acetate twice
10. washwashed with water and saturated brine
11. dry with materialdried over anhydrous sodium sulfate
12. concentrationconcentrated under reduced pressure
13. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0→9:1)

ORD record

ord-a6c709bc8aed4385b0ec563abf353830

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987445B2