79418-78-3

white to light yellow crystal powder

3-Fluoro-4-hydroxy-5-methoxybenzaldehyde is a reagent in the synthesis of series of caffeic acid phenethyl amide (CAPA) fluorinated derivatives.

General procedure for the synthesis of 3-fluoro-4-hydroxy-5-methoxybenzaldehyde using 2-fluoro-6-methoxy-4-methylphenol as starting material: substrate 1a (1 mmol), cobalt salt (n1 mol%), and NaOH (n2 equivalents) were dissolved in ethylene glycol (5 mL) and the reaction was stirred for 8 hr at 80°C under oxygen (1 atm) atmosphere. Upon completion of the reaction, hydrochloric acid (10 mL, 2%) and methyl tert-butyl ether (MTBE, 10 mL) were sequentially added to the reaction mixture. The organic layer was separated and the aqueous phase was further extracted with MTBE (10 mL × 2). The organic phases were combined, dried with anhydrous sodium sulfate and concentrated to give the residue. The residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate, 10/1) to give the target product 2a.

[1] Tetrahedron Letters, 2014, vol. 55, # 8, p. 1406 - 1411
[2] Green Chemistry, 2014, vol. 16, # 5, p. 2807 - 2814
[3] Green Chemistry, 2014, vol. 16, # 3, p. 1248 - 1254