反应详情

In a glass duplicated reactor, equipped with a shaft stirrer, reflux condenser, inlet tube and blow valve, 2.00 kg of betulin diacetate of example 5 was dissolved under stirring in the mixture of 10 l of toluene and 8 l of ethanol containing 700 g of potassium hydroxide. The reaction mixture was refluxed for 2 hours, then under heating filtered through a PP cloth and the filtrate was inoculated with pure betulin crystals. After cooling down, the crystallized betulin was filtered off on a processing filter, washed with 3 l of ethanol, 3 l of 50% ethanol and 30 l of boiling water and finally 5 l of boiling distilled water. The crystalline betulin was dried in a hot-air oven at the temperature of 70-75° C. for the period of 48 h. 1.12 kg (66%) of betulin in the form of fine crystalline power was obtained, having the m.p. 256-258° C., [α]D+16 (10% v/v CH3OH in CHCl3; 0.35 g/100 ml), which has the HPLC purity of 98.9-99.1%. 1H NMR spectrum of the obtained betulin measured in CDCl3 with the addition of 10% v/v CD3OD is as follows: 0.76 s, 0.83 s, 0.97 s, 0.98 s, 1.02 s, 1.68 s, 6×3H (6×CH3); 2.39 ddd, 1H (J′=10.98, J″=10.8, J′″5.8, H-19β); 3.19 dd, 1H (J′=11.1, J″=5.2, H-3α); 3.33 dd, 1H (J′=11.0, J″=1.2, H-28a); 3.80 dd, 1H, (J′=10.8, J″=1.8, H-28b); 4.58 m, 1H (ΣJ=6.5, H-29E); 4.68 m, 1H (ΣJ=2.9, H-29Z). 13C NMR spectrum of the obtained betulin measured in CDCl3 with the addition of 10% v/v CD3OD is as follows: 14.74, 15.34, 15.96, 16.09, 18.28, 19.07, 20.81, 25.19, 27.02, 27.37, 27.97, 29.15, 29.73, 33.95, 34.21, 37.14, 37.29, 38.69, 38.84, 40.90, 42.70, 47.77, 47.77, 48.74, 50.38, 55.27, 60.53, 78.97, 109.68, 150.46. By concentrating the mother liquor to the final volume of 8 l was after inoculation and cooling down obtained a second fraction of the crystalline betulin, which was also filtered on a processing filter and washed in the same way as the first fraction. After drying in the hot-air oven at the temperature of 70-75° C. for the period of 48 h further 0.46 kg (27%) of the second fraction of betulin was obtained, having the m.p. 256-257° C., [α]D+16 (10% v/v CH3OH in CHCl3; 0.35 g/100 ml), which, according to HPLC analysis, has the purity of 98.7-99.0%. The overall yield of the hydrolysis is thus 1.58 kg of betulin (93%).

1. customequipped with a shaft stirrer
2. temperaturereflux condenser, inlet tube and blow valve
3. temperatureThe reaction mixture was refluxed for 2 hours
4. temperatureunder heating
5. filtrationfiltered through a PP cloth
6. temperatureAfter cooling down
7. filtrationthe crystallized betulin was filtered off on a processing
8. filtrationfilter
9. washwashed with 3 l of ethanol, 3 l of 50% ethanol and 30 l of boiling water and finally 5 l
10. distillationof boiling distilled water
11. dry with materialThe crystalline betulin was dried in a hot-air oven at the temperature of 70-75° C. for the period of 48 h