Réaction #1869170

Équation de réaction

2-Methoxyestradiol

Compound 1

2-Methoxyestradiol

Aluminum isopropoxide

cyclohexanone

→

product

Rendement 78.0%

2-methoxyestra-1,3,5(10)-trien-17-one

Rendement 78.0%

Solvants

sodium bicarbonate

Conditions de réaction

Traitement

1. 1
   Autrethat was equipped with a 25 mL Dean-Stark trap and a reflux condenser
2. 2
   TempératureThe entire apparatus had been flame
3. 3
   Autredried under an argon atmosphere
4. 4
   workup.ADDITIONToluene (400 mL) was added
5. 5
   workup.DISSOLUTIONto dissolve the starting material
6. 6
   Autrethe entire reaction mixture
7. 7
   Températurewas heated
8. 8
   Températureat reflux (145°-150° C.) for 20 h
9. 9
   ExtractionThe organic material was extracted with dichloromethane (3×300 mL)
10. 10
    Autreseparated
11. 11
    Extractionthe aqueous layer was extracted with ethyl acetate (2×75 mL)
12. 12
    SéchageThe combined organic extracts were dried over magnesium sulfate and condensed
13. 13
    Autrea rotary evaporator
14. 14
    AutreThe cyclohexanone and cyclohexanol were removed by vacuum distillation
15. 15
    TempératureWhen the distillation pot was cool enough
16. 16
    workup.ADDITIONhexane was added
17. 17
    Autre2-methoxyestrone (Scheme 1, Compound 4) precipitated out of solution

Mode opératoire

2-Methoxyestradiol (Scheme 1, Compound 1) (10 g, 33.1 mmol) was placed in a 1 L round bottom flask that was equipped with a 25 mL Dean-Stark trap and a reflux condenser. The entire apparatus had been flame dried under an argon atmosphere. Toluene (400 mL) was added to dissolve the starting material. Aluminum isopropoxide (34.6 g, 169 mmol) and cyclohexanone (135 mL, 1.3 mol) were added and the entire reaction mixture was heated at reflux (145°-150° C.) for 20 h. Saturated aqueous sodium bicarbonate solution (200 mL) was added after the reaction mixture was allowed to cool to room temperature. The organic material was extracted with dichloromethane (3×300 mL). The aqueous emulsion was acidified with 3 N HCl (˜20 mL) until the emulsion separated and the aqueous layer was extracted with ethyl acetate (2×75 mL). The combined organic extracts were dried over magnesium sulfate and condensed using a rotary evaporator. The cyclohexanone and cyclohexanol were removed by vacuum distillation. When the distillation pot was cool enough, hexane was added and 2-methoxyestrone (Scheme 1, Compound 4) precipitated out of solution. 7.72 g (25.7 mmol, 78%) of product was obtained. 1H NMR (300 MHz, CDCl3) δ 6.81 (s, 1H), 6.68 (s, 1H), 5.46 (s, 1H), 3.88 (s, 3H), 2.89-2.76 (m,2H), 2.61-1.24 (m, 13H), 0.94 (s, 3H).

Source