Process for the production of artemisinin intermediates
View Patent ↗This application relates to a process for the production of (2R)-dihydroartemisinic acid or (2R)-dihydroartemisinic acid esters from artemisinic acid or artemisinic acid esters, respectively, by diimine hydrogenation of the exocyclic CC-double bond, and use of said process in the production of the antimalarial drug artemisinin.
1. A process for the preparation of a compound of the formula I
wherein R1 is hydrogen or linear or branched alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms,
comprising reacting a compound of the formula III
with diimine, wherein the diimine is prepared in situ.
2. A process as claimed in claim 1 wherein the diimine is generated from hydroxylamine and hydroxylamine O-sulfonic acid in the presence of a base.
3. A process as claimed in claim 1 wherein the diimine is generated from hydroxylamine-O-sulfonic acid in the presence of a base.
4. A process as claimed in claim 1 wherein the diimine is generated from hydroxylamine and an acetic acid ester.
5. A process as claimed in claim 1 wherein the diimine is generated from hydrazine and an oxidant.
6. A process as claimed in claim 1 wherein the diimine is generated from acid-catalyzed decarboxylation of azodicarboxylate.
7. A process according to any of claims 1 or 2 to 6 , further comprising oxidizing the compound of the formula I to artemisinin II