Hydrochloric Acid → 17-Allyl-3,14beta-dihydroxy-4,5alpha-epoxy-6beta-methylaminomorphinan

HRID 1740882Notes

Reaction equation

HRID 1740882 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.CN.[C:29]([BH3-])#[N:30].[Na+].Cl>CO>[CH2:3]([N:4]1[CH2:5][CH2:6][C@:7]23[C:8]4[C:13]5[O:14][C@H:15]2[C@@H:16]([NH:30][CH3:29])[CH2:18][CH2:19][C@@:20]3([OH:23])[C@H:21]1[CH2:22][C:9]=4[CH:10]=[CH:11][C:12]=5[OH:24])[CH:2]=[CH2:1].[CH2:3]([N:4]1[CH2:5][CH2:6][C@:7]23[C:8]4[C:13]5[O:14][C@H:15]2[C@H:16]([NH:30][CH3:29])[CH2:18][CH2:19][C@@:20]3([OH:23])[C@H:21]1[CH2:22][C:9]=4[CH:10]=[CH:11][C:12]=5[OH:24])[CH:2]=[CH2:1]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5003444Sodium cyanoborohydrideHCID 5464092Naloxone HydrochlorideHCID 6364545Methylamine hydrochloride

Product 2

HCID 5424824217-Allyl-3,14beta-dihydroxy-4,5alpha-epoxy-6beta-methylaminomorphinanYield 24%HCID 5424824317-Allyl-3,14beta-dihydroxy-4,5alpha-epoxy-6alpha-methylaminomorphinanYield 12%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Naloxone hydrochloride (3.0 g), methylamine hydrochloride (5.57 g) and sodium cyanoborohydride (0.33 g) were suspended in anhydrous methanol (40 ml) and stirred for 17 hours at room temperature. After addition of concentrated hydrochloric acid (1.0 ml) and removal of solvent by distillation, distilled water (50 ml) was added followed by washing with chloroform (20 ml). Saturated aqueous sodium bicarbonate (10 ml) was added to make the solution basic followed by extraction with chloroform (30 ml×3). After drying with anhydrous magnesium sulfate, the solvent was distilled off. The resulting crude product was purified with silica gel column chromatography (Merck 7734 100 g; ethyl acetate/methanol/aqueous ammonia=90/10/1→80/20/2) to obtain the target compound in the form of a pure fraction (91 0.4 g, 12%; 92 0.8 g, 24%).

Workup

  1. distillationby distillation
  2. distillationdistilled water (50 ml)
  3. additionwas added
  4. washby washing with chloroform (20 ml)
  5. additionSaturated aqueous sodium bicarbonate (10 ml) was added
  6. extractionbasic followed by extraction with chloroform (30 ml×3)
  7. dry with materialAfter drying with anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off
  9. customThe resulting crude product was purified with silica gel column chromatography (Merck 7734 100 g; ethyl acetate/methanol/aqueous ammonia=90/10/1→80/20/2)

Sources & evidence

ORD record
ord-1fcf3e7f9d1d4622b880baa9ec39144a
Source dataset
uspto-grants-1999_10
Patent number
US05972953

Reaction notes

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