Reacción #1853315

Ecuación de reacción

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

Disolventes

acetone

acetonitrile

acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONmixed with a solution
2. 2
   workup.STIRRINGThe mixture was stirred for 45 h at rt
3. 3
   Otroprecipitated DCU
4. 4
   Otroremoved by filtration
5. 5
   Concentraciónthe solution concentrated under reduced pressure
6. 6
   Otroto give a dark-brown oil
7. 7
   workup.ADDITIONThe brown oil containing crude 3-1
8. 8
   Temperaturacooled in an ice bath for 2 h
9. 9
   Filtraciónfiltered
10. 10
    Otroto remove
11. 11
    Otroprecipitated DCU
12. 12
    ConcentraciónThe filtrate was concentrated to dryness
13. 13
    workup.ADDITIONThe fractions containing 3-1
14. 14
    Concentraciónconcentrated to dryness
15. 15
    workup.ADDITIONThe residue was treated with 20 mL acetone
16. 16
    Filtraciónfiltered
17. 17
    Otroto remove
18. 18
    Otroprecipitated DCU
19. 19
    ConcentraciónThe filtrate was concentrated to dryness under reduced pressure
20. 20
    Otroto yield partially
21. 21
    Otropurified 3-1

Procedimiento

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.

Fuente