反应详情

温度

30 °C

Toluene (118 g), sodium triacetoxyborohydride (44.5 g) were mixed at 0° C. to room temperature. To this mixture was charged a premixed toluene solution of 6-methoxy-8-(1-piperazinyl)quinoline (Step 1, 160 g, 27.4 wt % in toluene) and 1-(5-fluoroquinolin-8-yl)piperidin-4-one (Step 3, 41 g). The resulting mixture was stirred for 2 to 3 hours at about 30° C. KOH solution (443 g 9% in water) was charged to quench the residual sodium triacetoxyborohydride. Heptane (118 g) was added to further precipitate the product. The product was then filtered and washed with ethanol (2×100 ml). Yield 68 g, 86%. This crude product (67 g) was dissolved in 586 g dichloromethane and passed through a charcoal/celite pad to remove palladium. The dichloromethane was distilled off while 400 g of ethanol was slowly added at the same time. The resulting slurry was filtered and washed with ethanol twice (65 g+100 g). The product was dried in oven at 55° C. overnight. Purification recovery yield 59.9 g, 89.4%.

1. customto quench the residual sodium triacetoxyborohydride
2. additionHeptane (118 g) was added to further precipitate the product
3. filtrationThe product was then filtered
4. washwashed with ethanol (2×100 ml)
5. dissolutionThis crude product (67 g) was dissolved in 586 g dichloromethane
6. customto remove palladium
7. distillationThe dichloromethane was distilled off while 400 g of ethanol
8. additionwas slowly added at the same time
9. filtrationThe resulting slurry was filtered
10. washwashed with ethanol twice (65 g+100 g)
11. customThe product was dried in oven at 55° C. overnight
12. customPurification recovery yield 59.9 g, 89.4%