反应详情

温度

45 °C

Crude 4-(3-fluorophenyl)butyric acid (8.83 kg) was added to concentrated sulfuric acid (30 kg) in a chemical reactor at a rate such that the pot temperature stayed between 40° C. and 60° C. (jacket heating was not necessary). The reaction was stirred at 45° C. for 3 hours and reaction completion was confirmed by LC. The reaction mixture was cooled and quenched with water (16 L), and then extracted with 35% THF in methylene chloride (25.8 kg). The organic layer was separated and washed with water (16 L), saturated aqueous NaHCO3 (16.9 kg) and then a mixture of water (16.1-kg)/brine (4.7-kg). The organic later was concentrated under vacuum and re-stripped with the aid of hexane to remove water and afford 6-fluoro-3,4-dihydro-2H-naphthalen-1-one as an oil (5.88 kg): MS (M+1)=165; H1 NMR (300 MHz): δ ppm (CDCl3): 2.14 (2H, m, J=6.03, 5.75 Hz), 2.64 (2H, dd, J=6.03, 5.75 Hz); 2.94 (2H, t, J=6.03), 6.9-7.0 (2H, m, J=2.26, 2.64, 6.03 Hz), 8.02-8.07 (1H, dd, J=6.03).

1. customstayed between 40° C. and 60° C.
2. temperatureheating
3. customreaction completion
4. temperatureThe reaction mixture was cooled
5. customquenched with water (16 L)
6. extractionextracted with 35% THF in methylene chloride (25.8 kg)
7. customThe organic layer was separated
8. washwashed with water (16 L), saturated aqueous NaHCO3 (16.9 kg)
9. additiona mixture of water (16.1-kg)/brine (4.7-kg)
10. concentrationThe organic later was concentrated under vacuum and re-stripped with the aid of hexane
11. customto remove water