Triethylamine → HCID 21480428, compound

Participants

Reaction Steps

3-carboxybenzaldehyde (Fluka; 12.01 g, 80 mmol) was slurried in 80 mL of dry toluene and thionyl chloride (7 mL, 96 mmol) and 5 drops of DMF. A reflux condenser with a calcium sulfate drying tube attached was placed on the flask. The mixture was refluxed for 1 hour after the solution went clear, and then allowed to cool. The volatiles were removed on the rotovap. The residue was pumped on briefly on a vacuum pump. The crude acid chloride was then dissolved in 150 mL of dry tetrahydrofuran, and cooled in an ice/water bath. N-methyl-3-fluoroaniline hydrochloride (13.05 g, 80.8 mmol) was added. Triethylamine (35 mL, 250 mmol) in 50 mL of dry tetrahydrofuran was then added dropwise via an addition funnel. The cloudy solution was allowed to warm to room temperature over 1 hour, and allowed to stir overnight. To remove the copious amount of precipitate, 100 mL of diethyl ether was added and the reaction mixture was filtered. After rinsing the salts with more ether, the solvents were removed under reduced pressure. The residue was extracted with ethyl acetate, washed with 1N HCl twice, then with water, sodium carbonate solution, and saturated NaCl solution. The organic layer was dried over sodium sulfate/magnesium sulfate, and the solvent removed by evaporation at reduced pressure. Crude N-(3-fluorophenyl)-3-formyl-N-methylbenzamide as a light golden oil was obtained, 19.92 g (96% unchromatographed yield) [NMR (300 MHz, DMSO-d6): δ 3.38 (s, 3H); 6.94-7.02 (m, 2H); 7.18-7.29 (m, 2H); 7.46 (t, J=7.7 Hz, 1H) 7.55 (d, J=7.6 Hz, 1H); 7.81 (m, 2H); 9.90 (s, 1H)].

Provenance & Evidence