Methanol → 6-Methyloximino-17-methyl-4,5alpha-epoxy-3,14-dihydroxymorphinan

HRID 478018Notes

Reaction equation

HRID 478018 reaction equation
[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3=[CH:8][CH:9]=[C:10]([OH:22])[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]=43)[CH2:4][CH2:3]1)=O.Cl.C[O:25][NH2:26].[OH-].[Na+].[CH3:29]O>O>[CH3:29][CH:14]1[C:16](=[N:26][OH:25])[CH2:17][C@:18]2([OH:21])[C@:5]34[CH2:4][CH2:3][N:2]([CH3:1])[C@@H:19]2[CH2:20][C:7]2[CH:8]=[CH:9][C:10]([OH:22])=[C:11]([O:12][C@@H:13]13)[C:6]4=2

Participants

6

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 521874O-Methylhydroxylamine hydrochlorideHCID 5284604Oxymorphone

Product 1

HCID 867422916-Methyloximino-17-methyl-4,5alpha-epoxy-3,14-dihydroxymorphinan

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of oxymorphone (0.9 g, 3 mmol) and O-methyl hydroxylamine hydrochloride (0.33 g, 3.9 mmol) in 15 mL MeOH containing 1.6 mL of 10% aqueous NaOH was refluxed for 5 h, cooled, diluted with water (approximately 100 mL) and extracted with 150 mL CHCl3 (3×50 mL). The combined extracts were dried (MgSO4), and evaporated. The residue obtained was recrystallized from CH2Cl2 -hexane to yield 0.84 g on the product. It was further purified by flash column chromatography on silica gel, eluting with EtOAc-EtOH-NH40H (100:1:1) (approx. size 40 microns). The combined fractions were evaporated in vacuo and the residue obtained was recrystallized from hexane-petroleum ether. Yield: 0.4 g (40%). mp 115-116 C. IR: (KBr): No C=O absorption at 1730 cm-1. 1H NMR (CDCl3) δ 4.92 (s,C5H), 3.85 (s, OCH3) Rf: silica gel 60 in EtOAc-EtOH-NH40H (100:1:1) 0.30. Anal. Calcd for: C18H22N2O4C, 65.44; H, 6.71; N, 8.48. Found: C, 65.51; H, 6.74; N, 8.46.

Workup

  1. temperaturecooled
  2. extractionextracted with 150 mL CHCl3 (3×50 mL)
  3. dry with materialThe combined extracts were dried (MgSO4)
  4. customevaporated
  5. customThe residue obtained
  6. customwas recrystallized from CH2Cl2 -hexane
  7. customto yield 0.84 g on the product
  8. customIt was further purified by flash column chromatography on silica gel
  9. washeluting with EtOAc-EtOH-NH40H (100:1:1) (approx. size 40 microns)
  10. customThe combined fractions were evaporated in vacuo
  11. customthe residue obtained
  12. customwas recrystallized from hexane-petroleum ether
  13. customIR: (KBr): No C=O absorption at 1730 cm-1

Sources & evidence

ORD record
ord-16f305ddaea1486d98d4c47fffbffeb3
Source dataset
uspto-grants-1989_12
Patent number
US04889860

Reaction notes

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