Reaktion #1853315

Reaktionsgleichung

oxycodone

Cbz-L-Glu(OtBu)-OH

DCC

HOBt

oxycodone

DIEA

→

2-(benzyloxycarbonylamino)-pentanedioic acid 5-tert-butyl ester 1-(3-methoxy-14-hydroxy-6,7-didehydro-4,5α-epoxy-17-methylmorphinan-6-yl) ester

Lösungsmittel

acetone

acetonitrile

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONmixed with a solution
2. 2
   workup.STIRRINGThe mixture was stirred for 45 h at rt
3. 3
   Sonstigeprecipitated DCU
4. 4
   Sonstigeremoved by filtration
5. 5
   Einengenthe solution concentrated under reduced pressure
6. 6
   Sonstigeto give a dark-brown oil
7. 7
   workup.ADDITIONThe brown oil containing crude 3-1
8. 8
   Temperaturcooled in an ice bath for 2 h
9. 9
   Filtrationfiltered
10. 10
    Sonstigeto remove
11. 11
    Sonstigeprecipitated DCU
12. 12
    EinengenThe filtrate was concentrated to dryness
13. 13
    workup.ADDITIONThe fractions containing 3-1
14. 14
    Einengenconcentrated to dryness
15. 15
    workup.ADDITIONThe residue was treated with 20 mL acetone
16. 16
    Filtrationfiltered
17. 17
    Sonstigeto remove
18. 18
    Sonstigeprecipitated DCU
19. 19
    EinengenThe filtrate was concentrated to dryness under reduced pressure
20. 20
    Sonstigeto yield partially
21. 21
    Sonstigepurified 3-1

Vorschrift

A solution comprised of oxycodone free base, 1-1, (517 mg, 1.64 mmol), DIEA (1.5 mL, 8.6 mmol) in 9 mL of anhydrous acetonitrile was stirred at rt for 20 min and mixed with a solution containing DMAP (400 mg, 3.3 mmol), DCC (1.01 g, 4.1 mmol), and HOBt (440 mg, 3.3 mmol) in 6 mL of anhydrous acetonitrile. Cbz-L-Glu(OtBu)-OH (1.1 g, 3.3 mmol) was then added to the combined solutions. The mixture was stirred for 45 h at rt, precipitated DCU removed by filtration, and the solution concentrated under reduced pressure to give a dark-brown oil. HPLC analysis indicated that 39% of the oxycodone had been converted to 3-1. The brown oil containing crude 3-1 was dissolved in 20 mL of acetone, cooled in an ice bath for 2 h, and filtered to remove precipitated DCU. The filtrate was concentrated to dryness, and subjected to flash chromatography using a gradient of 0–10% methanol in DCM. The fractions containing 3-1 were combined and concentrated to dryness. The residue was treated with 20 mL acetone and filtered to remove precipitated DCU. The filtrate was concentrated to dryness under reduced pressure to yield partially purified 3-1.

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