反应详情

温度

45 °C

A mixture of concentrate sulfuric acid (10.21 kg) and crude 4-(3,5-difluoro-phenyl)-butyric acid (2.8 kg) was stirred at 45° C. until the cyclization reaction was complete by HPLC. The reaction mixture was diluted with water (6.15 kg), and the product was extracted with THF/methylene chloride (2.71/7.33 kg) mixture. The organic layer was sequentially washed with water (4 liters), saturated aqueous sodium bicarbonate (2.64 kg), water (3.0 kg) and 50% diluted brine (8.4 kg). Removal of the solvents provided 1.64 kg (62% yield) of 6,8-difluoro-3,4-dihydro-2H-naphthalen-1-one as a light yellow solid (92.75% pure by HPLC): MP=58.1-58.8° C.; MS (M+1)=183; H1 NMR (300 MHz): δ (DMSO): 2.00 (2H, p, J=6.4 Hz), 2.57 (2H, t, J=6.40 Hz), 2.96 (2H, t, J=6.40 Hz), 7.08-7.20 (2H, m, J=2.26 Hz).

1. extractionthe product was extracted with THF/methylene chloride (2.71/7.33 kg) mixture
2. washThe organic layer was sequentially washed with water (4 liters), saturated aqueous sodium bicarbonate (2.64 kg), water (3.0 kg) and 50% diluted brine (8.4 kg)
3. customRemoval of the solvents