Reacción #66630

Ecuación de reacción

3,4-dimethoxy-benzaldehyde

ethylmagnesium bromide

→

4-cyclopropyl-1,2-dimethoxy-benzene

Disolventes

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroat −78° C
2. 2
   Temperaturawarmed to 2° C. until the reaction color
3. 3
   Otro(15 minutes)
4. 4
   Temperaturato warm up to room temperature over 1.5 hours
5. 5
   OtroSolvent was removed under reduced pressure, and dichloromethane (20 ml)
6. 6
   workup.ADDITIONwas added
7. 7
   TemperaturaThe reaction mixture was cooled to 0° C.
8. 8
   Temperaturato warm up to room temperature over 30 minutes
9. 9
   Otroquenched with saturated ammonium chloride solution
10. 10
    FiltraciónThe mixture was filtered through celite
11. 11
    LavadoThe combined dichloromethane was washed with saturated aqueous solution of ammonium chloride, saturated aqueous sodium bicarbonate and brine
12. 12
    SecadoThe organic phase was dried over anhydrous sodium sulfate
13. 13
    Concentraciónconcentrated under reduced pressure
14. 14
    OtroThe residue was purified by silica gel chromatography (gradient: 8% to 30% ethyl acetate in hexane)

Procedimiento

To a solution of zirconocene dichloride (1.76 g, 6.02 mmols) in dry tetrahydrofuran (25 ml), was slowly added ethylmagnesium bromide (12 ml, 1 M in tetrahydrofuran, 12 mmol) at −78° C. The green solution was stirred for 15 minutes at −78° C. and then warmed to 2° C. until the reaction color turned red (15 minutes). A solution of 3,4-dimethoxy-benzaldehyde (1.00 g, 6.02 mmol) in dry tetrahydrofuran (20 ml) was added and the reaction was allowed to warm up to room temperature over 1.5 hours. Solvent was removed under reduced pressure, and dichloromethane (20 ml) was added. The reaction mixture was cooled to 0° C. and titanium chloride (IV) (6 ml, 1M in dichloromethan, 6 mmol) was added. The reaction was allowed to warm up to room temperature over 30 minutes, and quenched with saturated ammonium chloride solution. The mixture was filtered through celite and portioned between dichloromethane and water. The combined dichloromethane was washed with saturated aqueous solution of ammonium chloride, saturated aqueous sodium bicarbonate and brine. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (gradient: 8% to 30% ethyl acetate in hexane) to yield 4-cyclopropyl-1,2-dimethoxy-benzene as yellow oily residue (0.2 g, 19%). Ref: Vincent Gandon et al. Eur. J. Org. Chem. 2000, 3713.

Fuente