Process for production of intermediates for use in cefalosporin synthesis
AssigneeSandoz Ltd.
InventorsJohannes Ludescher, Hubert Sturm, Katja Vorndran
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Abstract
The invention relates to a new process for the production of intermediates for the synthesis of caephalosporin of formula (I) wherein R1, R2 and R3, independently of one another, are alkyl, alkenyl, aryl, hydroxy(C1-6)alkyl, carbamoyl-(C1-6)alkyl, amino-(C1-6)alkyl, acylamino-(C1-6)alkyl or carboxy(C1-6)alkyl, or wherein R2 and R3 together with the adjacent nitrogen atom, form an alicyclic 5- to 8-membered heterocyclic ring, and R1 signifies alkyl, alkenyl or aryl. The process according to the invention is notable in that the formation of undesired by-products, especially Δ2-analogous compounds of formula (I), is greatly reduced.
Claims11
A process for the production of a compound of formula
- wherein R1, R2 and R3, independently of one another, are alkyl, alkenyl, aryl, hydroxy(C1-6)alkyl, carbamoyl-(C1-6)alkyl, amino-(C1-6)alkyl, acylamino-(C1-6)alkyl or carboxy-(C1-6)alkyl, or wherein
- R2 and R3 together with the adjacent nitrogen atom, form an alicyclic 5- to 8-membered heterocyclic ring, which, in addition to the nitrogen atom, may also contain a further 1 or 2 hetero atoms selected from the group consisting of oxygen and sulphur, and R1 signifies alkyl, alkenyl or aryl, as well as for the production of acid addition salts and/or hydrates of a compound of formula I,
- comprising the reaction steps
- a) desilylation of a compound of formula
- wherein R4 is a silyl-protecting group, by adding a protic solvent, in order to obtain a compound of formula
- b) reaction of the compound of formula III obtained in step a) with an organic base of formula
- wherein R1, R2 and R3 have the significances indicated above, in order to obtain a compound of formula I.
A process for the production of cefepime of formula
- or one of its acid addition salts or hydrates comprising the reaction steps
- a) desilylation of a compound of formula
- wherein R4 is a silyl-protecting group, by adding a protic solvent, in order to obtain a compound of formula
- b) reaction of the compound of formula III obtained in step a) with a strong organic I base of formula
- in order to obtain a compound of formula
- c) optional conversion of a compound of formula IA, as obtained from step b), into the form of an acid addition salt or a hydrate, and
- d) acylation of the 7-amino group of a compound of formula IA obtained from step b) or of its acid addition salt or hydrate obtained from step c), in order to obtain cefepime of formula V.
Dependencies are inferred from the claim text.