96516-31-3

96516-32-4

96516-31-3

1. To a solution of 2-chloro-3-fluorobenzoic acid (1.00 g, 5.73 mmol) in tetrahydrofuran (THF, 40 ml) was slowly added borane-tetrahydrofuran complex (1.0 M solution, 20.1 ml, 20.1 mmol) at 0 °C. The reaction mixture was stirred under reflux conditions overnight. After completion of the reaction, the mixture was cooled with crushed ice. 2. 1N aqueous hydrochloric acid and ethyl acetate (AcOEt) were added to the cooled reaction mixture to separate the organic and aqueous layers. The organic layer was dried with anhydrous sodium sulfate (Na2SO4) and subsequently concentrated under reduced pressure to give the crude product of (2-chloro-3-fluorophenyl)methanol. 3. To a solution of oxalyl chloride (737 μl, 8.60 mmol) in dichloromethane (CH2Cl2, 50 ml) was slowly added dimethylsulfoxide (DMSO, 1.22 ml, 17.2 mmol) dropwise at -78 °C. The mixture was stirred at the same temperature for 5 min. 4. (2-chloro-3-fluorophenyl) methanol obtained in step 2 was dissolved in dichloromethane (15 ml) and slowly added to the above reaction mixture at -78°C. The reaction solution was warmed to -40°C and stirred for 1 hour. 5. Triethylamine (3.97 ml, 28.7 mmol) was added to the reaction mixture with continued stirring and gradually warmed to room temperature. After completion of the reaction, 0.5N aqueous hydrochloric acid was added and the organic and aqueous layers were separated. 6. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate (Na2SO4). The solvent was removed under reduced pressure and the crude product was purified by column chromatography (eluent: n-hexane/ethyl acetate = 50:1) to give 2-chloro-3-fluorobenzaldehyde (500 mg, 55% yield). 7. The product was analyzed by 1H NMR. 7. The product was confirmed by 1H NMR (CDCl3): δ 7.35-7.43 (2H, m), 7.72-7.78 (1H, m), 10.47 (1H, s).