Bromomethylcyclopropane → Buprenorphine component OF alks-5461

Participants

Reaction Steps

In an illustrative embodiment, a mixture of norbuprenorphine, a mild base, and cyclopropylmethyl bromide are heated in an oilbath at about 80-100° C. until the reaction is substantially complete. The reaction mixture is then added over 5 minutes to 160 ml of water, with mechanical stirring, yielding a gum. The mixture is stirred and filtered, and the filter cake is washed with water. The HPLC will show about 90% by area of desired product, and 0.2-0.5% of an N-butenyl substituted impurity. The resulting product is dried, and then boiled in alcohol, cooled, and filtered to yield buprenorphine.

Provenance & Evidence