Preparation of 7,10-di:alkoxy-10-deacetyl-baccatin compounds

• Main Authors: DIDIER ERIC, PAUZE DENIS, ODDON GILLES
• Format: Patent
• Language: English; French
• Published: 21.05.1999
• Edition: 6
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

Process for simultaneous alkylation of the 7- and 10-OH groups of 10-deacetylbaccatin compounds of formula (V) in a single step comprises using an alkylating agent selected from alkyl halides and sulphates and oxonium salts in the presence of one or more anionisation agents such as strong bases in an anhydrous medium. A = H or a group of formula (i) or (ii); G = OH-protecting group; R1 = (a) 1-8C alkyl, 2-8C alkenyl, 2-8C alkynyl or 3-6C cycloalkyl; (b) phenyl or alpha - or beta -naphthyl (both optionally substituted); or (c) 5-membered heteroaryl containing one or more N, O and S and optionally substituted; provided that the alkyl substituents and alkyl parts of other substituents in (b) and (c) have 1-4 C atoms, the alkenyl and alkynyl substituents have 2-8 C atoms and the aryl substituents are phenyl or naphthyl; R2 = benzoyl (optionally substituted) or COOR2'; R2' = 1-8C alkyl, 2-8C alkenyl, 3-8C alkynyl, 3-6C cycloalkyl, 4-6C cycloalkenyl or 7-10C bicycloalkyl, phenyl or alpha - or beta -naphthyl or saturated 4-6C heterocyclyl (all optionally substituted); R3, R4 = H, alkyl, aryl, halogen, alkoxy, aralkyl, alkoxyaryl, haloalkyl or haloaryl; or R3+R4 = 4- to 7-membered ring. La présente invention concerne un nouveau procédé de préparation de dérivés dialkoxylés de la classe des taxoïdes par alkylation directe des deux positions 7 et 10 de la désacétylbaccatine ou des dérivés estérifiés en position 13 de cette dernière.