Methane → Hydrocodone

In this Example, 8,14-dihydro-thebaine (6.00 g, 19.14 mmol) was mixed with 24 ml of approx. 6 N Hydrochloric acid (144 mmol, prepared by mixing concentrated hydrochloric acid (12 ml) with DI water (12 ml)) at room temperature with stirring. The homogeneous light yellow colored solution was stirred for 4 hours. Thin Layer chromatography on silica gel plates 90:10:1 (dichloromethane:methanol: concentrated ammonium hydroxide) indicated that the reaction was complete. Decolorizing charcoal (Darco, 0.3 g) was added to the mixture and the reaction stirred for 20 minutes and then filtered. The charcoal was washed with DI water (2×5 ml). The combined acidic phases were cooled to <5° C. and the pH was adjusted to 9.64 with concentrated (28.0-30.0%) ammonium hydroxide solution (approx. 20 ml). The solid was filtered and washed with 2×10 ml of DI water. The product was dried at 60° C. under 22″ Hg vacuum until constant weight to give hydrocodone as a white amorphous said (4.87 g, 84.9% yield, 96.2 wt % by assay).

1. stirringThe homogeneous light yellow colored solution was stirred for 4 hours
2. stirringthe reaction stirred for 20 minutes
3. filtrationfiltered
4. washThe charcoal was washed with DI water (2×5 ml)
5. temperatureThe combined acidic phases were cooled to <5° C.
6. concentrationwith concentrated (28.0-30.0%) ammonium hydroxide solution (approx. 20 ml)
7. filtrationThe solid was filtered
8. washwashed with 2×10 ml of DI water
9. customThe product was dried at 60° C. under 22″ Hg vacuum until constant weight

ORD record

ord-d15a77c7de60436f844f29866a9184d8

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399671B2