Veratraldehyde → 4-Cyclopropyl-1,2-dimethoxybenzene

Temperature

-78 °C

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.

1. customat −78° C
2. temperaturewarmed to 2° C. until the reaction color
3. custom(15 minutes)
4. temperatureto warm up to room temperature over 1.5 hours
5. customSolvent was removed under reduced pressure, and dichloromethane (20 ml)
6. additionwas added
7. temperatureThe reaction mixture was cooled to 0° C.
8. temperatureto warm up to room temperature over 30 minutes
9. customquenched with saturated ammonium chloride solution
10. filtrationThe mixture was filtered through celite
11. washThe combined dichloromethane was washed with saturated aqueous solution of ammonium chloride, saturated aqueous sodium bicarbonate and brine
12. dry with materialThe organic phase was dried over anhydrous sodium sulfate
13. concentrationconcentrated under reduced pressure
14. customThe residue was purified by silica gel chromatography (gradient: 8% to 30% ethyl acetate in hexane)

ORD record

ord-3d491dee4d1142e2a0185486c55b5bef

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08524725B2