Hydrochloric Acid → Oxycodone Hydrochloride

HRID 2369252Notes

Reaction equation

HRID 2369252 reaction equation
[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:16][CH2:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15].C(O)C.[ClH:27].CN1[C@@H]2CC3C=CC(OC)=C4OC5C(C=C[C@]2(O)[C@]5(C=34)CC1)=O>O>[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:16][CH2:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15].[ClH:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 5284603OxycodoneHCID 5359420(4R,4aS,12bS)-4a-hydroxy-9-methoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one

Product 1

HCID 5462350Oxycodone HydrochlorideYield 85.12%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 25 mL flask was charged 2.0 g (6.34 mmol, from Example 9) of low ABUK oxycodone base, 6.4 mL of ethanol and 1.3 mL of water. The mixture was stirred at RT. The batch was heated to 41-46° C., added 0.643 g (6.527 mmol, 1.03 molar equivalents) of 37% hydrochloric acid, and a solution was then resulted. The mixture was heated to 55° C. and stirred at 55° C. for 10 hours to simulate the production salt formation timeframe. The mixture was cooled to room temperature and then to 0-5° C. The mixture was stirred at 0-5° C. for 1.5 hours, filtered, and the product on the filter was rinsed with cold ethanol (2.5 mL×2) and dried. 1.899 g of oxycodone HCl (85.12% yield, as Lot 2418-123) was obtained (2.5 ppm 14-hydroxycodeinone by LC/MS, undetected 8α,14-dihydroxy-7,8-dihydrocodeinone by LC/MS and 8β,14-dihydroxy-7,8-dihydrocodeinone by LC/MS; 0.01 HPLC A % 6-oxycodol; 99.93 HPLC A % oxycodone HCl).

Workup

  1. temperatureThe batch was heated to 41-46° C.
  2. customa solution was then resulted
  3. temperatureThe mixture was heated to 55° C.
  4. stirringstirred at 55° C. for 10 hours
  5. temperatureThe mixture was cooled to room temperature
  6. customto 0-5° C
  7. stirringThe mixture was stirred at 0-5° C. for 1.5 hours
  8. filtrationfiltered
  9. washthe product on the filter was rinsed with cold ethanol (2.5 mL×2)
  10. customdried

Sources & evidence

ORD record
ord-ccbe073b222e4f93bfc0828bb0c42914
Source dataset
uspto-grants-2014_04
Patent number
US08703950B2

Reaction notes

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