Patent ID: 6670507
Filing Date: 2003-12-30
Classification: C07C,C07D,Y02P

Abstract:
A process for the preparation of compounds of formula I and their physiologically acceptable salts, whereinR1 and R2 are, independently of one another, H, C1-C6alkyl, C1-C6halogenalkyl, C1-C6alkoxy, C1-C6alkoxy-C1-C6alkyl, or C1-C6alkoxy-C1-C6alkyloxy, R3 is C1-C6alkyl, R4 is C1-C6alkyl, and R5 is C1-C6alkyl, C1-C6hydroxyalkyl, C1-C6alkoxy-C1-C6-alkyl, C1-C6alkanoyloxy-C1-C6alkyl, C1-C6aminoalkyl, C1-C6alkylamino-C1-C6-alkyl, C1-C6-dialkylamino-C1-C6-alkyl, C1-C6-alkanoylamido-C1-C6-alkyl, HO(O)Câ€”C1-C6-alkyl, C1-C6alkyl-Oâ€”(O)Câ€”C1-C6alkyl, H2Nâ€”C(O)â€”C1-C6alkyl, C1-C6alkyl-HNâ€”C(O)â€”C1-C6alkyl or (C1-C6alkyl)2Nâ€”C(O)â€”C1-C6-alkyl, comprising the steps a) reaction of a compound of formula II, wherein R4 is as defined above, with a hydroxylamine of formula ZNHOH (III), wherein Z is a removable protecting group, to form a compound of formula IV, b) reaction of a compound of formula IV with a metal organic derivative of a compound of formula V, wherein R1, R2 and R3 are as defined above and Y is Cl, Br or I, to form a compound of formula VI, c) removal of the hydroxyl group to form a compound of formula VII, d) removal of the pseudoephedrine protecting group to form compounds of formula VIII, or performance of step d) before step c), or of steps c) and d) together in one reaction vessel, e) reaction of a compound of formula VIII with an amine of formula R5â€”NH2 to form a compound of formula IX f) removal of protecting group Z for the preparation of compounds of formula I.