Transition metal-catalyzed processes for the preparation of N-allyl compounds and use thereof

摘要

The present disclosure provides processes for the N-dealkylation of tertiary amines and the use of transition metal catalysts to prepare tertiary N-allyl amine derivatives and secondary amine derivatives thereof. The tertiary amines can be alkaloids and, more particularly, the tertiary amines can be opioids. In specific embodiments, the present disclosure provides methods for use in processes for the synthesis of naloxone and naltrexone from oripavine.

主权项

1. A method for making a compound of Formula (200)comprising
contacting a compound of Formula (45) with a compound of Formula (23) and a base in a first solvent to provide a compound of Formula (211)  and contacting the compound of Formula (211) with a transition metal catalyst and a second solvent to provide the compound of Formula (200); wherein:
X is selected from —Cl, —Br, and —I;R4, R5, R6, and R7 are each hydrogen;R14 and R16 are each independently selected from —OH, —H, and —OR17; R15 is selected from —OH, —H, —OR17, ═O, and ═CH2; andR17is an oxygen protecting group;V is a leaving group; andthe transition metal catalyst comprises a transition metal selected from the group consisting of Pd[0],Pd[II], Ni[0], and combinations of two or more thereof.