Synthesis of noroxymorphone from morphine

摘要

The present invention is directed to an improved process to convert morphine into noroxymorphone having economic and ecological advantages.

主权项

1. A process for producing noroxymorphone from morphine, comprising
reacting morphine of formula (II) to a compound of formula (IIIa) or (IIIb), wherein R1 and R1′ independently are a substituted or unsubstituted alkyl group with 1 to 20 carbon atoms or a substituted or unsubstituted aryl group, or a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, or a substituted or unsubstituted carbonyloxyalkyl group with 1 to 20 carbon atoms in the alkyl residue, or a substituted or unsubstituted carbonyloxyaryl group or a substituted or unsubstituted carbonyloxyalkylaryl group with 1 to 20 carbon atoms in the alkyl residue, or a silyl group of formula Si(R4)3, R4 are the same or different and are each a substituted or unsubstituted alkyl group having 1 to 6 carbon atoms or an unsubstituted or substituted phenyl group; reacting the compound of formula (IIIa) or (IIIb) to a compound of formula (IVa) or (IVb), respectively, wherein R1 and R1′ are defined as for the compound of formula (IIIa) and (IIIb), wherein the reaction of the compound of formula (IIIa) or (IIIb) to a compound of formula (IVa) or (IVb), is conducted by a Swern oxidation with pre-cooling; reacting the compound of formula (IVa) or (IVb) to a compound of formula (Va) or (Vb), respectively, wherein R1 and R1′ independently are a substituted or unsubstituted alkyl group with 1 to 20 carbon atoms or a substituted or unsubstituted aryl group, or a substituted or unsubstituted alkenyl group having 2 to 20 carbon atoms, or a substituted or unsubstituted carbonyloxyalkyl group with 1 to 20 carbon atoms in the alkyl residue, or a substituted or unsubstituted carbonyloxyaryl group or a substituted or unsubstituted carbonyloxyalkylaryl group with 1 to 20 carbon atoms in the alkyl residue, or a silyl group of formula Si(R4)3, R4 are the same or different and are each a substituted or unsubstituted alkyl group having 1 to 6 carbon atoms or an unsubstituted or substituted phenyl group, R2 is a substituted or unsubstituted aliphatic or aromatic acyl group with 1 to 20 carbon atoms; reacting the compound of formula (Va) or (Vb) to a compound of formula (VIa) or (VIb), respectively, wherein R1 and R1′ are defined as for the compound of formula (Va) and (Vb), wherein the reaction of the compound of formula (Va) or (Vb) to the compound of formula (VIa) or (VIb) is carried out with hydrogen peroxide and an organic acid, wherein the organic acid and the hydrogen peroxide are mixed and allowed to react for an induction time prior to addition to the compound of formula (Va) or (Vb); reacting the compound of formula (VIa) or (VIb) to a compound of formula (VIIa) or (VIIb), respectively, wherein R1 and R1′ are defined as for the compound of formula (VIa) and (VIb); and reacting the compound of formula (VIIa) or (VIIb) to noroxymorphone of formula (I),