Reaktion #578182

Reaktionsgleichung

sodium bicarbonate

daidzein

chloromethylmethyl ether

daidzein

diisopropylethylamine

daidzein

→

product

chromen-one

Lösungsmittel

dichloromethane

water

EtOAc hexane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeequipped with a thermocouple, overhead stirrer
2. 2
   Temperaturheating
3. 3
   workup.ADDITIONmantle, addition funnel and nitrogen line
4. 4
   SonstigeAn ice bath was removed
5. 5
   Temperaturto warm up to room temperature within 2 hours
6. 6
   TemperaturThe pot temperature was maintained at 40° C.
7. 7
   Sonstigereaction
8. 8
   Sonstigeusually overnight
9. 9
   TemperaturThe resulted clear brown solution was cooled to room temperature
10. 10
    Sonstigewas prepared in a 20 L plastic bucket
11. 11
    Sonstigeequipped with a powerful overhead stirrer
12. 12
    SonstigeThe organic phase was separated
13. 13
    Extraktionaqueous was back extracted with dichloromethane (2×1 L)
14. 14
    Waschenwashed with water (2×3 L), sodium bicarbonate (3 L)
15. 15
    Trocknendried over sodium sulfate (500 g)
16. 16
    SonstigeThe solvent was removed under reduced pressure

Vorschrift

A total of 329 g (1.29 mol) of 97% daidzein (from LLC Laboratories) was mixed with 4.5 L of dichloromethane in a 12 L 4-neck round bottom flask equipped with a thermocouple, overhead stirrer, heating mantle, addition funnel and nitrogen line. The resulted white suspension was chilled to 8° C., and a total of 655.8 g (5.07 mol, 3.9 eq.) of diisopropylethylamine (DIEA) was added to the pot. After 20 min a total of 373 g (4.63 mol, 3.59 eq.) of chloromethylmethyl ether (MOM-Cl) was added to the mixture via an addition funnel at 8° C. An ice bath was removed, replaced with a heating mantle and allowed to warm up to room temperature within 2 hours. The pot temperature was maintained at 40° C. and reaction was kept (usually overnight) at this temperature until daidzein and mono-MOM intermediate disappeared according to TLC (Rf=0.23 for daidzein, 0.38 for mono-MOM and 0.62 for bis-MOM-daidzein in EtOAc/hexane=1:1). The resulted clear brown solution was cooled to room temperature, and slowly poured under agitation on a cold mixture of 4 L of water, 1 kg of ice, 1 L of saturated sodium bicarbonate and 3 L of dichloromethane, which was prepared in a 20 L plastic bucket equipped with a powerful overhead stirrer and thermocouple. The pH of the resulted solution must stay basic during this work up to avoid degradation of the product. The organic phase was separated, and aqueous was back extracted with dichloromethane (2×1 L). The organic layers were combined, washed with water (2×3 L), sodium bicarbonate (3 L) and dried over sodium sulfate (500 g). The solvent was removed under reduced pressure to give 431 g (97% yield) of the product as a yellow solid. This material was purified by crystallization from 3.5 L of hot (56° C.) ethyl acetate followed by filtration and consequent washes with EtOAc/hexane=3:1 (2 L). Separated solid was dried overnight at 35° C. in a vacuum oven to yield 340.6 g (77% isolated yield) of bis-MOM-daidzein as a white solid. A second crop (a total of 66.31 g of the product) was isolated from a mother liquor to give a bis-MOM-daidzein in the 91.78% combined yield.

Quelle