Reaktion #311537

Reaktionsgleichung

3,14-dimethoxy-4,5α-epoxy-8α-methylmorphinan-6-one hydrochloride

3,14-Dimethoxy-4,5α-epoxy-8α-methylmorphinan-6-one Hydrochloride

cyclobutylmethyl bromide

sodium bicarbonate

→

desired compound

17-Cyclobutylmethyl-3,14-dimethoxy-4,5α-epoxy-8α-methylmorphinan-6-one

Lösungsmittel

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas heated at 105° to 100° C.
2. 2
   Temperaturmaintained under a nitrogen atmosphere
3. 3
   TemperaturThe reaction mixture was heated for 18 hours
4. 4
   Sonstigeafter which the inorganic material was removed by filtration
5. 5
   Waschenthe filter cake was washed twice with dimethylformamide (100 ml)
6. 6
   workup.DISTILLATIONdistilled under high vacuum (bath temperatures 35° C.)
7. 7
   workup.ADDITIONmade basic by the addition of saturated sodium bicarbonate solution
8. 8
   SonstigeAfter separating the organic layer
9. 9
   Extraktionthe aqueous phase was re-extracted with ethyl acetate (2×150 ml)
10. 10
    TrocknenThe combined ethyl acetate extracts were dried over MgSO4
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated under reduced pressure
13. 13
    Sonstigeto give 3.1 g (84% theory) of the crude desired product
14. 14
    SonstigeThis material was purified by chromatography on silica gel
15. 15
    workup.ADDITIONThose fractions containing pure product
16. 16
    Sonstigeevaporated

Vorschrift

A mixture of 3,14-dimethoxy-4,5α-epoxy-8α-methylmorphinan-6-one hydrochloride (4) (3.4 g, 9.29 mmol), cyclobutylmethyl bromide (3.4 g, 22.8 mmol), sodium bicarbonate (5.0 g, 59.5 mmol) and 100 milliliters of dimethylformamide was heated at 105° to 100° C. while being stirred and maintained under a nitrogen atmosphere. The reaction mixture was heated for 18 hours, after which the inorganic material was removed by filtration and the filter cake was washed twice with dimethylformamide (100 ml). The filtrate and washings were combined and distilled under high vacuum (bath temperatures 35° C.) and the material which remained was taken up with ethyl acetate (300 ml)/H2O (80 ml) and made basic by the addition of saturated sodium bicarbonate solution. After separating the organic layer, the aqueous phase was re-extracted with ethyl acetate (2×150 ml). The combined ethyl acetate extracts were dried over MgSO4, filtered and concentrated under reduced pressure to give 3.1 g (84% theory) of the crude desired product. This material was purified by chromatography on silica gel using benzene followed by 50:50 benzene/chloroform, chloroform and graded (2% to 50%) methanol/chloroform mixtures. Those fractions containing pure product were combined and evaporated to give 1.39 g (38% theory) of the desired compound as a foamy solid. A portion of the product was converted to the hydrochloride salt by treatment with ethereal hydrogen chloride.

Quelle