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

HRID 1857458Notes

Reaction equation

HRID 1857458 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-81f709acc4f14b248bbc70a034f06f68
Source dataset
uspto-grants-2000_11
Patent number
US06147084

Reaction notes

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