反应详情

温度

40 °C

248.3 g (content 232.7 g, 0.930 mol) of 8-(2-hydroxyethyl)-7-methoxy-2,2-dimethylchroman-4-one, 294.0 g (content 274.9 g, 1.098 mol) of the same compound and 7614 mL of ethyl acetate were put in a 15 L four-necked round bottom flask and stirred. Cooling of this suspension was started in a cold bath set to −4° C., and 161.9 g (1.574 mol) of sodium bromide, 508 mL of water, 3.17 g (20.28 mmol) of 2,2,6,6-tetramethylpiperidine oxide were put therein sequentially. After the inner temperature reached 0° C., a mixture of 5.536 mol of sodium hypochlorite solution and 2538 g of 7% (W/W) sodium hydrogen carbonate aqueous solution were added dropwise into the flask over about 2 hours. After the dropwise addition was completed, the temperature of the cooling bus was changed to 0° C. and stirring was continued for 45 minutes. The reaction mixture was transferred to a 20 L separatory funnel and the aqueous layer was discarded. The organic layer was washed with 2030 g of 10% sodium chloride aqueous solution and 2030 mL of water sequentially. The obtained organic layer was concentrated in vacuo (40° C.) and 743.7 g of slurry was obtained. 500 mL of DME was added to the obtained slurry to form a solution and concentrated in vacuo (40° C.) again and 500 mL of DME was added again to the precipitates so that they were dissolved. This solution was transferred to a 5 L four-necked round bottom flask and warmed in a 40° C. water bath. 515 mL of DME was further added and stirred at 183 rpm and about 500 mL of water was cast therein and cooling with an ice-water bath was started 4 minutes later. Seed crystals were added and the mixture was stirred for about 1 hour and 515 mL of water was further added over about 30 minutes. After stirring for about 1.3 hours, 1523 mL of heptane was further added over 1 hour and stirred at the same temperature for about 1 hour or more. Precipitated crystals were collected by filtration, washed with a mixture of DME/water/heptane [about 600 mL, DME/water/heptane=1/1/1.5]. The crystals were dried in vacuo (bath temperature: 40° C.) till the weight became almost constant and the title compound was obtained as a yellowish white solid.

1. temperatureCooling of this suspension
2. customwas started in a cold bath
3. customset to −4° C.
4. customreached 0° C.
5. additionwere added dropwise into the flask over about 2 hours
6. additionAfter the dropwise addition
7. customwas changed to 0° C.
8. stirringstirring
9. customThe reaction mixture was transferred to a 20 L separatory funnel
10. washThe organic layer was washed with 2030 g of 10% sodium chloride aqueous solution and 2030 mL of water sequentially
11. concentrationThe obtained organic layer was concentrated in vacuo (40° C.) and 743.7 g of slurry
12. customwas obtained
13. customto form a solution
14. concentrationconcentrated in vacuo (40° C.) again
15. addition500 mL of DME was added again to the
16. customprecipitates so that they
17. dissolutionwere dissolved
18. customThis solution was transferred to a 5 L four-necked round bottom flask
19. addition515 mL of DME was further added
20. stirringstirred at 183 rpm and about 500 mL of water
21. temperaturecooling with an ice-water bath
22. waitwas started 4 minutes
23. additionSeed crystals were added
24. stirringthe mixture was stirred for about 1 hour
25. addition515 mL of water was further added over about 30 minutes
26. stirringAfter stirring for about 1.3 hours
27. addition1523 mL of heptane was further added over 1 hour
28. stirringstirred at the same temperature for about 1 hour or more
29. customPrecipitated crystals
30. filtrationwere collected by filtration
31. washwashed with a mixture of DME/water/heptane [about 600 mL, DME/water/heptane=1/1/1.5]
32. customThe crystals were dried in vacuo (bath temperature: 40° C.) till the weight