反应详情

Formic acid (97-98%, 47.5 ml) is added dropwise to a cooled and stiffed mixture of estrone methyl ether (71.0 g) and 3-dimethylaminopropylamine (158 ml). The resulting mixture is heated in an oil bath (165°-175° C.) for 20 hours. The reaction is quenched in ice water (total volume 700 ml) and the resulting alkaline (pH--9) mixture is extracted twice with CH2Cl2. The combined extracts are washed with dilute aq. NAOH and with brine, dried (Na2SO4), filtered, and concentrated, Hexane (250 ml) is added to the residue and a white fluffy precipitate is filtered off, The solvent is removed, leaving a residual light brown oil which slowly crystallizes. A portion (20 g) of this material is chromatographed over silica gel (500 g) packed as a slurry in 7.5% of 10% NH4OH--CH3OH in CH2Cl2. The column is eluted (300 ml fractions) with the same solvent system. The desired material (about 14 g) is eluted in fractions 13-26 and pooled in CH2Cl2. As this solution stands at 20°-25°, crystals form. After two days, the crystals (4.803 g), mp 184°-192° C. with rapid heating, are collected by filtration. More crystals form in the filtrate and after 3 days these are collected. The compound can be recrystallized from methanol-acetone in the freezer, giving the second title compound as crystals, mp 184°-186° C. decomposition (dec) with bubbling.

1. temperaturea cooled
2. temperatureThe resulting mixture is heated in an oil bath (165°-175° C.) for 20 hours
3. customThe reaction is quenched in ice water (total volume 700 ml)
4. extractionthe resulting alkaline (pH--9) mixture is extracted twice with CH2Cl2
5. washThe combined extracts are washed with dilute aq. NAOH and with brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. additionHexane (250 ml) is added to the residue
10. filtrationa white fluffy precipitate is filtered off
11. customThe solvent is removed
12. customleaving a residual light brown oil which
13. customslowly crystallizes
14. customA portion (20 g) of this material is chromatographed over silica gel (500 g)
15. washThe column is eluted (300 ml fractions) with the same solvent system
16. washThe desired material (about 14 g) is eluted in fractions 13-26
17. customstands at 20°-25°
18. customcrystals form
19. filtrationthe crystals (4.803 g), mp 184°-192° C. with rapid heating, are collected by filtration
20. customMore crystals form in the filtrate and after 3 days
21. customthese are collected
22. customThe compound can be recrystallized from methanol-acetone in the freezer