Acetic Acid → 14-Hydroxydihydrocodeine

Participants

Reaction Steps

A mixture of dry 14-hydroxycodeinone (9.5 g dry) and damp 14-hydroxycodeinone (8.5 g by LOD) was charged to a reactor and triturated with water (150 g) (to enable blending) for 15 min. The resulting slurry was filtered and a sample of the cake dried at 50° C. under vacuum (0.39 g) for analysis. The remaining wet cake (assumed 17.5 g) was charged to a stainless steel Parr pressure vessel followed by water (48.37 g to give a total water of 54.84 g accounting for the water in the starting material) and acetic acid (7.21 g, 2.15 equivalents) forming a solution. Pd/C (10%, dry, 0.16 g, ˜0.01 g Pd/C per gram of 14-hydroxycodeinone) was then added under nitrogen, rinsing the sides of the flask with water (1.16 g, 0.07 g/g of 14-hydroxycodeinone). The resulting mixture was evacuated and the vacuum released with nitrogen three times. It was again evacuated and hydrogen was added with the mixture at 17° C. (target 20±5° C.) up to 40 psi (target 40±2 psi). There was a one degree change in temperature after 2 minutes. The temperature gradually crept up to 28° C. over 50 minutes. Heating was applied to the mixture after reaching 28° C., getting to 80±5° C., over 2 h. The reaction was held at 80±5° C./40 psi for approximately 18 h (total time of 21 h after hydrogen addition) and sampled (see table) showing 4.60 area % of 6α-oxycodol. Thus, it can be seen that the addition of hydrogen at low temperature gives relatively higher levels of 6α-oxycodol compared to adding hydrogen at a higher temperature.

Provenance & Evidence