Dimethylformamide → 3-(Bicyclo[2.2.1]hept-2-yloxy)-4-methoxybenzaldehyde

Temperature

80 °C

Isovanillin (50 g, 0.328 mol) is placed in a 1 liter round bottom flask which is equipped with a stir bar and reflux condensor and is charged with 500 ml of dimethylformamide. Potassium carbonate (45.3 g, 0.328 mol) is added to the reaction mixture which is heated to 80° C. At this temperature exo-2-bromonorbornane (12.57 g, 0.072 mol, 0.219 equivalents) is added and the reaction mixture is heated to 120° C. for 48 hours. The reaction is then cooled to room temperature and poured into 300 ml of water. The aqueous layer is extracted with ethyl ether (3×100 ml). The ethereal layer is washed with 1N sodium hydroxide solution (4×100 ml), water (3×100 ml) and saturated sodium chloride solution (3×100 ml). The organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield 15.47 g of a green/brown oil. The crude product is purified by flash chromatography using a gradient eluent system of ethyl acetate/hexane [10% ethyl acetate/hexane →20% ethyl acetate/hexane] to yield 7.76 g (14.4%) of the aldehyde as a white solid. MP: 75.5° C.-79.5° C.

1. customwhich is equipped with a stir bar
2. temperaturereflux condensor
3. temperaturethe reaction mixture is heated to 120° C. for 48 hours
4. temperatureThe reaction is then cooled to room temperature
5. extractionThe aqueous layer is extracted with ethyl ether (3×100 ml)
6. washThe ethereal layer is washed with 1N sodium hydroxide solution (4×100 ml), water (3×100 ml) and saturated sodium chloride solution (3×100 ml)
7. dry with materialThe organic layer is dried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD record

ord-f0f3a17104b343c2ab70cab59ba63c0f

Source dataset

uspto-grants-1994_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05294730