Phthalic Anhydride → HCID 11454029, compound

Participants

Reaction Steps

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.)

Provenance & Evidence