Formic Acid → Naltrexone Base

HRID 2387958Notes

Reaction equation

HRID 2387958 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].C(N(CC)CC)C.[CH:30]1(C=O)[CH2:32][CH2:31]1.C(O)=O>C(#N)C>[CH2:30]1[CH:32]([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])[CH2:31]1

Participants

6

Reactant 4

HCID 284Formic AcidHCID 8471TriethylamineHCID 123114CyclopropanecarboxaldehydeHCID 1528625314-Hydroxymorphine-6-one

Product 1

HCID 21159611Naltrexone BaseYield 95.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Into a round bottom flask was charged noroxymorphone (2.00 g, 0.007 moles), triethylamine (3.52 g, 0.035 mole, 4.85 mL), acetonitrile (15 mL), and cyclopropanecarboxaldehyde (0.98 g, 0.014 mole, 0.92 mL). The mixture was stirred for about 5 minutes at room temperature then >96% formic acid (4.0 g, 0.87 mole, 3.28 mL) was added dropwise. After stirring the mixture for 15 minutes at room temperature, dichloro(p-cymene)Ru(II) dimer (10 mg, 0.000014 moles) was added. The mixture was then stirred at room temperature for about 24 hours. HPLC indicated the reaction was complete. The reaction mixture was evaporated to a thick oil, and distilled water (5.0 mL) was added. The pH was adjusted to 9.4 using 29% NH3/H2O where a precipitate formed. The mixture was stirred overnight at room temperature. The precipitate was filtered, washed with distilled water (10 mL), and dried at 90° C. for about 24 hours. The dried precipitate yielded naltrexone base (2.28 g, 95% yield).

Workup

  1. stirringAfter stirring the mixture for 15 minutes at room temperature
  2. stirringThe mixture was then stirred at room temperature for about 24 hours
  3. customThe reaction mixture was evaporated to a thick oil
  4. distillationdistilled water (5.0 mL)
  5. additionwas added
  6. customformed
  7. stirringThe mixture was stirred overnight at room temperature
  8. filtrationThe precipitate was filtered
  9. washwashed with distilled water (10 mL)
  10. customdried at 90° C. for about 24 hours

Sources & evidence

ORD record
ord-71665ff699034196ad09d5d5f8baf60d
Source dataset
uspto-grants-2012_09
Patent number
US08269006B2

Reaction notes

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