2-Nitro-5-sulfanylbenzoic acid → (4R,4aS,12bS)-4a-hydroxy-9-methoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one

HRID 574358Notes

Reaction equation

HRID 574358 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].Cl.SC1C=CC([N+]([O-])=O)=C(C=1)C(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][CH:13]5[C:14]([CH:16]=[CH:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15]

Participants

3

Reactant 2

HCID 1236482-Nitro-5-sulfanylbenzoic acidHCID 5462350Oxycodone Hydrochloride

Product 1

HCID 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

Procedure

A sample of the oxycodone hydrochloride (579 mg, 1.65 mmol) was placed in an 8 mL reaction vial, to which was added 3.5 ml of the previously prepared solution of 5-mercapto-2-nitro-benzoic acid. The pH of the mixture was raised to 4.5 by addition of 100 mg/mL aqueous NaH2PO4 solution (0.47 mL), and a 1.0 ml aliquot was removed, diluted with pH 4.5, 0.01 M NaOAc/HOAc buffer solution (10 uL), and stirred. The remainder (2.5 mL) was reserved for separate spike experiments where known amounts of 14-hydroxycodeinone were added to the mixture. After 90 minutes, the pH was lowered to 2 with concentrated HCl (10 uL) and the suspension extracted with ethyl acetate (3×1 mL) by adding the solvent to the vial, capping it, and shaking vigorously. The organic layer was then completely removed from the vial by Pasteur pipet. The aqueous layer was analyzed by HPLC, wherein an analyte in the effluent stream was quantified from its absorbance at 325 nm. The 14-hydroxycodeinone content, and thus the sum of the 8-hydroxyoxycodone content and the 14-hydroxycodeinone content of the product of EXAMPLE 24, was 2.3 ppm as determined from a plot of the area under the 5-(oxycodone-8-sulfanyl)-2-nitro-benzoic acid peak per milligram of oxycodone analyzed versus the amount of 14-hydroxycodeinone added (ppm, i.e. microrams 14-hydroxycodeinone added per gram oxycodone) as shown in FIG. 11.

Workup

  1. customa 1.0 ml aliquot was removed
  2. additiondiluted with pH 4.5, 0.01 M NaOAc/HOAc buffer solution (10 uL)
  3. customfor separate spike experiments where known amounts of 14-hydroxycodeinone
  4. additionwere added to the mixture
  5. extractionthe suspension extracted with ethyl acetate (3×1 mL)
  6. additionby adding the solvent to the vial,
  7. stirringshaking vigorously
  8. customThe organic layer was then completely removed from the vial by Pasteur pipet
  9. additionadded
  10. addition(ppm, i.e. microrams 14-hydroxycodeinone added per gram oxycodone)

Sources & evidence

ORD record
ord-9d4c3d04943f4fb8972a26cf51bdbb7e
Source dataset
uspto-grants-2015_05
Patent number
US09034893B2

Reaction notes

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