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

HRID 845826Notes

Reaction equation

HRID 845826 reaction equation
[CH:1]1[C:6]2[CH2:7][C@H:8]3[N:13]([CH2:14][CH:15]4[CH2:17][CH2:16]4)[CH2:12][CH2:11][C@:10]45[C@H:18]([C:20]([CH2:22][CH2:23][C@@:9]34[OH:24])=O)[O:19][C:4]([C:5]=25)=[C:3]([OH:25])[CH:2]=1.Cl.C[O:28][NH2:29].Cl.[OH-].[Na+].[CH3:33]O>O>[CH3:33][CH:20]1[C:22](=[N:29][OH:28])[CH2:23][C@:9]2([OH:24])[C@:10]34[CH2:11][CH2:12][N:13]([CH2:14][CH:15]5[CH2:17][CH2:16]5)[C@@H:8]2[CH2:7][C:6]2[CH:1]=[CH:2][C:3]([OH:25])=[C:4]([O:19][C@@H:18]13)[C:5]4=2

Participants

6

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 521874O-Methylhydroxylamine hydrochloride2×HCID 5485201Naltrexone Hydrochloride

Product 1

HCID 1317156456-Methyloximino-17-cyclopropylmethyl-4,5alpha-epoxy-3,14-dihydroxymorphinan

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Naltrexone hydrochloride (1.134 g, 3 mmol) was added to a solution of CH3ONH2HCl (0.33 g, 3.9 mmol) in 15 mL MeOH containing 3.2 mL 10% aqueous NaOH. The mixture was refluxed for 5 h, cooled, diluted with approximately 100 mL H2O and extracted with 150 mL CHCl3 (3×50 mL). The combined CHCl3 extracts were dried (MgSO4) and evaporated. TLC showed that the reaction was incomplete and hence the reaction was repeated as before using the mixture, CH3ONH2HCl (0.165 g, 1.9 mmol) and 0.8 mL of 10% aqueous NaOH. After workup the product was chromatographed on a column of silica gel (approx. size 40 microns) using EtOAC-EtOH-NH4OH (100:1:0.5) as eluent. The fractions were combined, evaporated and the residue recrystallized from hexane-petroleum ether. Yield: 0.55 g (49.6%). mp 172°-173° C. IR (KBr): No C=O absorption at 1720 cm-1 ; 1H NMR: (CDCl3)δ4.95 (s, C5H), 3.82 (s, OCH3); Rf: silica gel 60 in EtOAc-EtOH-NH4OH (100:1:1) 0.40. Anal. Caled for C21H26N2O4 : C, 68.09; H, 7.07; N, 7.56. Found: C, 67.96; H, 7.11; N, 7.55.

Workup

  1. temperatureThe mixture was refluxed for 5 h
  2. temperaturecooled
  3. extractionextracted with 150 mL CHCl3 (3×50 mL)
  4. dry with materialThe combined CHCl3 extracts were dried (MgSO4)
  5. customevaporated
  6. customwas chromatographed on a column of silica gel (approx. size 40 microns)
  7. customevaporated
  8. customthe residue recrystallized from hexane-petroleum ether
  9. customIR (KBr): No C=O absorption at 1720 cm-1

Sources & evidence

ORD record
ord-35fde9e90d08493f9cc615afdf27ecb2
Source dataset
uspto-grants-1988_07
Patent number
US04760069

Reaction notes

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