646032-89-5Relevant articles and documents
Synthesis of 1-Chloronaloxone and 2-Chloronaloxone
Brailey-Partridge, James,Carey, John S.,Lovell, Christopher J.,Taylor, George M.
, p. 2502 - 2507 (2021/11/01)
This paper describes the unambiguous synthesis of authentic samples of 1-chloronaloxone and 2-chloronaloxone to support the unequivocal assignment of impurities observed in a drug product containing a combination of buprenorphine hydrochloride and naloxone hydrochloride. The key step in the synthesis of 1-chloronaloxone was the C-1-selective chlorination of (5α)-6-(1,3-dioxolan-2-yl)-4,5-epoxy-14-hydroxy-3-methoxy-17-(2-propenyl)morphinan using the Palau’Chlor reagent. The key step in the synthesis of 2-chloronaloxone was the C-2-selective chlorination of (5α)-3-diethylcarbamate-6-(1,3-dioxolan-2-yl)-4,5-epoxy-14-hydroxy-17-(2-propenyl)morphinan using a directed ortho metalation approach.
PROCESS FOR THE PREPARATION OF MORPHINE ANALOGS VIA THE REACTION OF ORGANOMETALLIC REAGENTS WITH AN OXAZOLIDINE DERIVED FROM MORPHINANS
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Paragraph 0084, (2013/08/15)
The oxazolidine derived from the reaction of oxymorphone with the Burgess reagent, temporariiy protected at 0-3 and C-6, reacts with Grignard or other suitable metallic or organometallic reagents to directly provide, for example, A/-allyl, A/-methylcyclopropyl and /V-methylcyclobutyl derivatives that are further converted into naltrexone, naloxone, nalbuphone and nalbuphine in excellent yields. These morphine analogs can be prepared from the oxazolidine in a one- pot synthesis.
