Cyclopropanecarboxaldehyde → Naltrexone

HRID 2387960Notes

Reaction equation

HRID 2387960 reaction equation
[CH3:1][N:2]1[C@@H:12]2[CH2:13][C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[C:16]4[O:21][C@H:6]5[C:7]([CH:9]=[CH:10][C@:11]2([OH:22])[C@:5]5([C:15]=34)[CH2:4][CH2:3]1)=[O:8].[CH:23]1(C=O)[CH2:25][CH2:24]1.C([O-])=O.[NH4+]>C(O)(C)C>[CH2:23]1[CH:25]([CH2:1][N:2]2[C@@H:12]3[CH2:13][C:14]4[CH:19]=[CH:18][C:17]([OH:20])=[C:16]5[O:21][C@H:6]6[C:7]([CH2:9][CH2:10][C@:11]3([OH:22])[C@:5]6([C:15]=45)[CH2:4][CH2:3]2)=[O:8])[CH2:24]1

Participants

5

Reactant 3

HCID 123114CyclopropanecarboxaldehydeHCID 2723923Ammonium formateHCID 1528625314-Hydroxymorphine-6-one

Product 1

HCID 5360515NaltrexoneYield 91%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A round bottom flask was charged with noroxymorphone (2.19 g, 0.008 moles), isopropanol (20 mL), and cyclopropanecarboxaldehyde (1.07 g, 0.02 moles, 0.91 mL). Ammonium formate (2.40 g, 0.038 moles) was added. To this solution was added RuCl3 (anhydrous)(10 mg, 0.05 mmole). The reaction mixture was stirred at room temperature for 24 h. HPLC analysis indicated the reaction was complete. To the reaction mixture was added distilled water (1.0 mL) and the mixture was stirred for 16 h at room temperature. Then, the reaction mixture was transferred to a round bottom flask and evaporated under reduced pressure leaving a semi solid. To the semi solid was added distilled water (10 mL). To this solution was added 29% NH3/H2O (˜5 mL) adjusting the pH from 7.0 to 9.4. A white precipitate formed. The precipitate was filtered, washed with distilled water (10 mL), and dried for 16 h at 95° C. yielding (−)-naltrexone (2.35 g, 0.007 moles, 91% yield) as an off white solid.

Workup

  1. additionTo the reaction mixture was added
  2. distillationdistilled water (1.0 mL)
  3. stirringthe mixture was stirred for 16 h at room temperature
  4. customThen, the reaction mixture was transferred to a round bottom flask
  5. customevaporated under reduced pressure
  6. customleaving a semi solid
  7. additionTo the semi solid was added
  8. distillationdistilled water (10 mL)
  9. additionTo this solution was added 29% NH3/H2O (˜5 mL)
  10. customA white precipitate formed
  11. filtrationThe precipitate was filtered
  12. washwashed with distilled water (10 mL)
  13. customdried for 16 h at 95° C.

Sources & evidence

ORD record
ord-06f09e11e4714322b7f4dbb26975ed13
Source dataset
uspto-grants-2012_09
Patent number
US08269006B2

Reaction notes

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