Hydrochloric Acid → 5-(3,3-Dimethylbutyl)thiophene-2-carbaldehyde

Temperatur

-78 °C

To a solution of thiophene (300 mg, 3.57 mmol) in anhydrous 10% hexamethylphosphoramide in tetrahydrofuran (33 mL) under argon at −78° C. was added n-butyllithium (1.57 mL, 2.5 M in hexanes) dropwise. After stirring at −78° C. for 1 hour, 1-chloro-3,3-dimethylbutane (430 mg, 3.57 mmol) was added dropwise and the resulting solution allowed to warm to room temperature over 3 hours. The reaction mixture was re-cooled to −78° C., a second portion of n-butyllithium (1.78 mL, 4.46 mmol) was added dropwise over 5 minutes and the mixture was stirred for 1 hour at −78° C. before anhydrous dimethylformamide (1.38 mL, 17.8 mmol) was added dropwise and the resulting mixture allowed to warm to room temperature. The reaction mixture was poured into 1 N hydrochloric acid (150 mL) and organics were extracted with ether (3×100 mL), dried with magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel with gradient elution (5%→20% ethyl acetate in hexanes) to give 5-(3,3-dimethylbutyl)thiophene-2-carbaldehyde (130 mg, 19%). Used without further characterization.

1. temperatureto warm to room temperature over 3 hours
2. temperatureThe reaction mixture was re-cooled to −78° C.
3. additionwas added dropwise
4. temperatureto warm to room temperature
5. extractionorganics were extracted with ether (3×100 mL)
6. dry with materialdried with magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by flash chromatography on silica gel with gradient elution (5%→20% ethyl acetate in hexanes)

ORD-Eintrag

ord-217d810fc451467987b2a2654e9fb484

Quelldatensatz

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09315495B2