Potassium Carbonate → 3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-difluoromethoxy-3-hydroxybenzaldehyde (10 g, 53 mmol) and potassium carbonate (44 g, 105 mmol) in tetrahydrofuran (100 mL) is cooled to 0° C. and a solution of bromomethylcyclopropane (11 mL, 116.6 mmol) in tetrahydrofuran (50 mL) is added under vigorous stirring. The reaction mixture is heated to reflux under stirring for 7 hours, then fresh bromomethylcyclopropane (5.5 mL, 58.3 mmoles) is added and heating is continued for further 7 hours. The reaction mixture is cooled to room temperature and 2 N sodium hydroxide (100 ml) is added; the aqueous layer is extracted with dichloromethane (2×100 mL), the combined organic layers are dried over Na2SO4 and the solvent is removed under reduced pressure to afford 3-cyclopropylmethoxy-4-difluoromethoxybenzaldehyde (12 g), that is used in the next step without further purification.

Provenance & Evidence