申请人:Pfizer Inc.
公开号:US20020198375A1
公开(公告)日:2002-12-26
The process of the present invention and the preparation of the compound of the present invention are illustrated in the following reaction schemes. Except where otherwise indicated, in the reaction schemes and discussion that follow, substituents R
1
, R
2
, R
3
, L, A
1
, A
2
and X are as defined above unless otherwise described.
This invention relates to a novel process for the preparation of
3
-cyclic-ether-substituted cephalosporins of formula I
1
wherein the group CO
2
R
1
is a carboxylic acid or a carboxylate salt and R
2
has the formula:
2
wherein
A
1
is selected from the group consisting of C
6-10
aryl, C
1-10
heteroaryl and C
1-10
heterocyclyl;
A
2
is selected from the group consisting of hydrogen, C
1-6
alkyl, C
3-10
cycloalkyl, C
6-10
aryl, C
1-6
alkyl(CO)(C
1-6
)alkyl-O—, HO(CO)(C
1-6
)alkyl, mono-(C
6-10
aryl)(C
1-6
alkyl), di-(C
6-10
aryl)(C
1-6
alkyl) and tri-(C
6-10
aryl)(C
1-6
alkyl);
from a zwitterionic compound of formula II; or from a compound of formula V:
3
wherein R
2
is as defined above and R
3
is para-nitrobenzyl or allyl.
The invention also relates to the preparation of the above compounds of formulae II and V.
本发明涉及一种新型的制备公式I1中的3-环氧基取代头孢菌素的方法,其中羧酸基CO2R1是羧酸或羧酸盐,R2具有公式2,其中A1选自C6-10芳基,C1-10杂芳基和C1-10杂环基的群;A2选自氢,C1-6烷基,C3-10环烷基,C6-10芳基,C1-6烷基(CO)(C1-6)烷基-O-,HO(CO)(C1-6)烷基,单-(C6-10芳基)(C1-6烷基),双-(C6-10芳基)(C1-6烷基)和三-(C6-10芳基)(C1-6烷基)的群;在反应方案和讨论中,除非另有说明,取代基R1,R2,R3,L,A1,A2和X与上述定义相同。此外,本发明还涉及制备公式II和V中上述化合物的方法。其中公式II为一种双离子化合物,公式V为一种化合物,其中R2如上所述,R3为对硝基苯甲基或丙烯基。