Cyclopropanecarboxaldehyde → Naltrexone Base

HRID 2387959Notes

Reaction equation

HRID 2387959 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+]>[Ru](Cl)(Cl)Cl.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][CH: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

6

Reactant 3

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

Product 1

HCID 21159611Naltrexone BaseYield 91%

Reagents, catalysts & solvents 2

HCID 61850Ruthenium trichlorideCatalystHCID 3776IsopropanolSolvent

Procedure

Into a round bottom flask was added noroxymorphone (2.19 g, 0.008 mole), cyclopropanecarboxaldehyde (1.07 g, 0.015 mole, 1.00 mL), ammonium formate (2.40 g, 0.038 mole), and isopropanol (20 mL, HPLC grade). After stirring for about 5 minutes, ruthenium (III) chloride (10 mg) was added. The mixture was stirred under nitrogen at room temperature for about 48 hours. HPLC indicated the reaction was complete. To the dark solution, distilled water (1 mL) was added and this mixture stirred for about 18 hours at room temperature. The entire mixture was evaporated under reduced pressure to a thick paste. Distilled water (10 mL) was added and the pH was adjusted to 9.4 from 7.0 using 29% NH3/H2O where a precipitate formed. The precipitate was filtered, washed with distilled water (10 mL), and dried overnight at 90° C. The dried precipitate yielded naltrexone base (2.35 g, 91% yield) as an off white solid.

Workup

  1. stirringThe mixture was stirred under nitrogen at room temperature for about 48 hours
  2. distillationTo the dark solution, distilled water (1 mL)
  3. additionwas added
  4. stirringthis mixture stirred for about 18 hours at room temperature
  5. customThe entire mixture was evaporated under reduced pressure to a thick paste
  6. additionDistilled water (10 mL) was added
  7. customformed
  8. filtrationThe precipitate was filtered
  9. washwashed with distilled water (10 mL)
  10. customdried overnight at 90° C

Sources & evidence

ORD record
ord-6d101de4991241a387cf6fbe02147aae
Source dataset
uspto-grants-2012_09
Patent number
US08269006B2

Reaction notes

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