Naltrexone → (5α,6α)-17-(Cyclopropylmethyl)-4,5-epoxy-6-(methylamino)morphinan-3,14-diol

HRID 651049Notes

Reaction equation

HRID 651049 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.[CH3:27][NH2:28].[H][H]>CO.[Pt]=O>[CH:15]1([CH2:14][N:13]2[CH2:12][CH2:11][C@:10]34[C:5]5[C:4]6[O:19][C@H:18]3[C@@H:20]([NH:28][CH3:27])[CH2:22][CH2:23][C@@:9]4([OH:24])[C@H:8]2[CH2:7][C:6]=5[CH:1]=[CH:2][C:3]=6[OH:25])[CH2:17][CH2:16]1

Participants

6

Reactant 3

HCID 5360515NaltrexoneHCID 6364545Methylamine hydrochlorideHCID 178418361HCID 178418361, compound

Product 1

HCID 15908858(5α,6α)-17-(Cyclopropylmethyl)-4,5-epoxy-6-(methylamino)morphinan-3,14-diolYield 79.5%

Reagents, catalysts & solvents 2

HCID 82844Platinum oxide (PtO)CatalystHCID 887MethanolSolvent2×

Procedure

Naltrexone (1.0 g) and methylamine hydrochloride (0.99 g, 5 equivalents) were dissolved in methanol (15 ml) followed by stirring for 20 minutes at room temperature. This reaction solution was added to platinum oxide (0.05 g, 5 w %) in methanol (10 ml) activated in advance in a hydrogen atmosphere followed by hydrogenation for 4 hours at room temperature and atmospheric pressure. The catalyst was removed by Celite filtration and the solvent was distilled off. After adding saturated aqueous sodium bicarbonate (20 ml) and extracting with chloroform (20 ml×2), the extract was washed with saturated brine and dried with anhydrous sodium sulfate, and the solvent was distilled off. The resulting dark reddish-violet oily substance was dissolved in chloroform (2 ml) followed by addition of ethyl acetate (4 ml) to obtain the target compound (0.83 g, yield: 79%) by crystallization. A portion of this compound was removed and various spectra were measured in the form of a hydrochloride.

Workup

  1. waitfollowed by hydrogenation for 4 hours at room temperature
  2. customThe catalyst was removed by Celite filtration
  3. distillationthe solvent was distilled off
  4. additionAfter adding saturated aqueous sodium bicarbonate (20 ml)
  5. extractionextracting with chloroform (20 ml×2)
  6. washthe extract was washed with saturated brine
  7. dry with materialdried with anhydrous sodium sulfate
  8. distillationthe solvent was distilled off
  9. dissolutionThe resulting dark reddish-violet oily substance was dissolved in chloroform (2 ml)
  10. additionfollowed by addition of ethyl acetate (4 ml)

Sources & evidence

ORD record
ord-7b5115f1ba784954b95d487802d57024
Source dataset
uspto-grants-2001_08
Patent number
US06277859B1

Reaction notes

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