2,6-Dimethyl-4-fluorobenzoic acid

Synthesis

14659-60-0

16633-50-4

General procedure for the synthesis of 2,6-dimethyl-4-fluorobenzoic acid from methyl 2,6-dimethyl-4-fluorobenzoate: 4-amino-2,6-dimethylbenzoic acid (200 mg, 1.1 mmol) was heated and reacted with NOBF4 (196 mg, 1.7 mmol) in 1,2-dichlorobenzene at 100 °C for 30 min. Upon completion of the reaction, the reaction solution was cooled to room temperature and subsequently diluted with methanol and water. A few potassium hydroxide pellets (2-3 pellets) were added to the solution and the mixture was heated to reflux for 16 hours. At the end of the reaction, the solution was concentrated. The residue was partitioned between ether and 1N sodium hydroxide solution. The aqueous layer was extracted with ether. The aqueous layer was cooled to 0°C and acidified with concentrated hydrochloric acid to pH=1-2. The acidified aqueous layer was extracted with dichloromethane. The organic layers were combined and dried over anhydrous sodium sulfate. The dried organic layer was filtered and concentrated to give 58 mg (31% yield) of the target product 2,6-dimethyl-4-fluorobenzoic acid as a brown solid.

References