Phthalic Anhydride → HCID 11454029, compound

HRID 1766132Notes

Reaction equation

HRID 1766132 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:24]1(=[O:34])[O:29][C:27](=[O:28])[C:26]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:25]12>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[CH3:23][O:22][C:10]1[CH:9]=[CH:8][C:7]2[CH2:20][C@H:19]3[N:2]([CH3:1])[CH2:3][CH2:4][C@:5]45[C:6]=2[C:11]=1[O:12][C@H:13]4[C:14](=[O:15])[CH2:16][CH2:17][C@@:18]35[O:21][C:24](=[O:34])[C:25]1[C:26](=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:27]([OH:29])=[O:28]

Participants

5

Reactant 2

HCID 6811Phthalic AnhydrideHCID 5284603Oxycodone

Product 1

HCID 11454029HCID 11454029, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

A solution comprised of oxycodone free base, 1-1, (63 mg, 0.2 mmol), phthalic anhydride (1.185 g, 8.0 mmol) and DMAP (24 mg, 0.2 mmol) in 10 mL of pyridine was stirred in an oil bath at 50–55° C. for 24 h and concentrated under reduced pressure. The residue was subjected to silica gel flash chromatography with a 5%–20% methanol in dichloromethane gradient. The fraction containing 2-1 was collected and concentrated under reduced pressure. HPLC indicated that the fraction was 60% pure. The concentrated fraction was subjected to another silica gel flash chromatography using a gradient of 0–20% methanol in dichloromethane as eluent to yield a fraction containing 32 mg (35% yield) of 96% pure (HPLC) 2-1, which was further purified by HPLC. The 1H and 13C NMR spectra verified the structure of 2-1 as a hydrogen phthalate ester of the 14-hydroxyl group of oxycodone. (The absence of an 1H resonance in the region of 5.5–6 ppm for a C7 vinylic proton, and the presence of a 13C resonance at 207.5 ppm for the C6 carbonyl group excluded the presence of an enol ester linkage in 2-1.)

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe fraction containing 2-1
  3. customwas collected
  4. concentrationconcentrated under reduced pressure
  5. customto yield a fraction
  6. additioncontaining 32 mg (35% yield) of 96% pure (HPLC) 2-1, which
  7. customwas further purified by HPLC

Sources & evidence

ORD record
ord-fd6827ad55d0494ca8e4549884d843cd
Source dataset
uspto-grants-2007_06
Patent number
US07230005B2

Reaction notes

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