Isopropanol → Oxycodone

HRID 1410418Notes

Reaction equation

HRID 1410418 reaction equation
[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([O:20]C)=[CH:15][CH:16]=[C:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1.C(OO)(=[O:26])C.CC(O)C>C(O)=O.C(O)(=O)C.[Pd]>[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:15][CH2:16][C@:17]2([OH:26])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:20]

Participants

7

Reactant 3

HCID 3776IsopropanolHCID 6585Peracetic AcidHCID 5324289Thebaine2×

Product 1

HCID 5284603Oxycodone

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent2×HCID 284Formic AcidSolvent2×

Procedure

Thebaine (100 g, 0.321 mol) was dissolved in formic acid (100 g) and acetic acid (100 g); volume 253 ml. Solution 2: Peracetic acid (39% in acetic acid, 63.25 g, 0.325 mol) was diluted with acetic acid to give a solution of 85 ml volume. The two solutions were pumped through the continuous flow reactor in the ratio 6 ml/min solution 1 to 2 ml/min solution 2 at 20° C. (4 min residence time). An analytical control after the continuous reactor showed less than 4% Thebaine remaining. The continuous stream was added directly to the hydrogenation autoclave that was precharged with 2-propanol (60 g), formic acid (98-100%, 10 g) and 5% Pd/C (2.5 g) and held at 100° C. under H2 (40 bar). The hydrogenation was stirred for 16 h. After the hydrogenation, the catalyst was filtered off and the crude mixture was either basified with NaOH to obtain the low impurity Oxycodone base, or treated with HCl in 2-Propanol to give the Oxycodone HCl. The yields were 74% for the base and 73% for the HCl salt. The 14-hydroxy-codeinone content of the base was 27 ppm and of the HCl salt <10 ppm.

Workup

  1. customto give a solution of 85 ml volume
  2. custom(4 min residence time)
  3. additionThe continuous stream was added directly to the hydrogenation autoclave that
  4. customheld at 100° C. under H2 (40 bar)
  5. filtrationAfter the hydrogenation, the catalyst was filtered off

Sources & evidence

ORD record
ord-b4e9cb4526bb4132a1550a1b111056d7
Source dataset
uspto-grants-2014_12
Patent number
US08921557B2

Reaction notes

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