Dicyclohexylcarbodiimide → HCID 68453063, compound

HRID 1766133Notes

Reaction equation

HRID 1766133 reaction equation
[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:16][CH2:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15].CCN(C(C)C)C(C)C.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[NH:58]([C:72]([O:74][CH2:75][C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=1)=[O:73])[C@H:59]([C:69](O)=[O:70])[CH2:60][CH2:61][C:62](=[O:68])[O:63][C:64]([CH3:67])([CH3:66])[CH3:65]>C(#N)C.CN(C1C=CN=CC=1)C.CC(C)=O>[CH3:23][O:22][C:10]1[CH:9]=[CH:8][C:7]2[CH2:20][C@H:19]3[N:2]([CH3:1])[CH2:3][CH2:4][C@:5]45[C:6]=2[C:11]=1[O:12][C@H:13]4[C:14]([O:15][C:69](=[O:70])[CH:59]([NH:58][C:72]([O:74][CH2:75][C:76]1[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=1)=[O:73])[CH2:60][CH2:61][C:62]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:68])=[CH:16][CH2:17][C@@:18]35[OH:21]

Participants

9

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1074725-tert-Butyl N-((phenylmethoxy)carbonyl)-L-glutamateHCID 5284603Oxycodone2×

Product 1

HCID 68453063HCID 68453063, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 180AcetoneSolventHCID 6342AcetonitrileSolvent2×

Procedure

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.

Workup

  1. additionmixed with a solution
  2. stirringThe mixture was stirred for 45 h at rt
  3. customprecipitated DCU
  4. customremoved by filtration
  5. concentrationthe solution concentrated under reduced pressure
  6. customto give a dark-brown oil
  7. additionThe brown oil containing crude 3-1
  8. temperaturecooled in an ice bath for 2 h
  9. filtrationfiltered
  10. customto remove
  11. customprecipitated DCU
  12. concentrationThe filtrate was concentrated to dryness
  13. additionThe fractions containing 3-1
  14. concentrationconcentrated to dryness
  15. additionThe residue was treated with 20 mL acetone
  16. filtrationfiltered
  17. customto remove
  18. customprecipitated DCU
  19. concentrationThe filtrate was concentrated to dryness under reduced pressure
  20. customto yield partially
  21. custompurified 3-1

Sources & evidence

ORD record
ord-5e87b609a1dd4b3bb2da46e70be211f6
Source dataset
uspto-grants-2007_06
Patent number
US07230005B2

Reaction notes

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