6-FLUOROGRAMINE

399-51-9

50-00-0

124-40-3

343-93-1

An aqueous solution of about 40% dimethylamine (35.68 kg, 1.0 eq.) was added to a 250 L reaction vessel under nitrogen protection and the mixture was cooled to about 4.5 °C. Glacial acetic acid (43.4 kg, 2.5 eq.) was slowly added dropwise over a period of 140 minutes while the reaction temperature was controlled to not exceed 15°C. After the dropwise addition was completed, stirring was continued for 20 minutes at about 3°C. Subsequently, 37% formaldehyde aqueous solution (25.9 kg, 1.1 eq.) was slowly added over about 20 minutes, keeping the reaction temperature between 0°C and 10°C. Upon addition of 6-fluoroindole (39.2 kg), the reaction was exothermic raising the temperature to about 40°C and subsequently cooled to about 20°C. The reaction solution was slowly transferred to a 650 L reactor filled with 3M NaOH aqueous solution, taking about 40 minutes. The resulting suspension was stirred at 5°C to 20°C for 40 minutes, the product was collected by filtration, washed with deionized water (120 kg) and dried at 50°C to afford 1-(6-fluoro-1H-indol-3-yl)-N,N-dimethylmethylamine (45.4 kg, 85% yield).