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

HRID 845824Notes

Reaction equation

HRID 845824 reaction equation
[CH2:1]=[CH:2][CH2:3][N:4]1[C@@H:21]2[CH2:22][C:9]3[CH:10]=[CH:11][C:12]([OH:24])=[C:13]4[O:14][C@H:15]5[C:16]([CH2:18][CH2:19][C@:20]2([OH:23])[C@:7]5([C:8]=34)[CH2:6][CH2:5]1)=O.Cl.Cl.C[O:28][NH2:29].[OH-].[Na+].[CH3:32]O>O>[CH3:32][CH:16]1[C:18](=[N:29][OH:28])[CH2:19][C@:20]2([OH:23])[C@:7]34[CH2:6][CH2:5][N:4]([CH2:3][CH:2]=[CH2:1])[C@@H:21]2[CH2:22][C:9]2[CH:10]=[CH:11][C:12]([OH:24])=[C:13]([O:14][C@@H:15]13)[C:8]4=2

Participants

6

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 521874O-Methylhydroxylamine hydrochlorideHCID 5464092Naloxone Hydrochloride

Product 1

HCID 867422936-Methyloximino-17-allyl-4,5alpha-epoxy-3,14-dihydroxymorphinan

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of naloxone hydrochloride (1.09 g, 3 mmol) and O-methylhydroxylamine hydrochloride (0.33 g, 3.9 mmol) in 15 mL MeOH was stirred overnight. After the addition of 3.2 mL of 10% aqueous NaOH, the mixture was refluxed for 5 h. It was cooled, diluted with approx. 100 mL of water, and extracted with 150 mL CHCl3 (3×50 mL). The combined extracts were dried (MgSO4) and evaporated. The residue obtained was recrystallized from hexane-petroleum ether. Yield 0.8 g, (75%) mp 128-129° C. IR (KBr): No C=O absorption at 1717 cm-1 ; H NMR (CDCl3): δ4.95 (s, C5H), 3.82 (s, OCH3). Rf: silica gel 60 in EtOAc-EtOH-NH4OH (100:1:1) 0.50. Anal. Calcd for C20H24N2O4 : C, 67.40; H, 6.79; N, 7.86. Found: C, 67.27; H, 6.84; N, 7.82.

Workup

  1. temperaturethe mixture was refluxed for 5 h
  2. temperatureIt was cooled
  3. extractionextracted with 150 mL CHCl3 (3×50 mL)
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. customevaporated
  6. customThe residue obtained
  7. customwas recrystallized from hexane-petroleum ether
  8. customIR (KBr): No C=O absorption at 1717 cm-1

Sources & evidence

ORD record
ord-935cd597118a43b18f82732d3410455b
Source dataset
uspto-grants-1988_07
Patent number
US04760069

Reaction notes

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