PROCESS FOR THE PREPARATION OF DERIVATIVES OF 1-(2-FLUORO[1,1'-BIPHENYL]-4-YL)-CYCLOPROPANECARBOXYLIC ACID

摘要

The present invention relates to a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof:;wherein R represents one or more groups independently selected from fluorine, chlorine, bromine, and iodine,said process comprising the cyclopropanation of a compound of formula (II) with ethylene carbonate or ethylene sulfate:;wherein X is chlorine, bromine, iodine or a triflate group (CF3SO3) or a group; wherein R is as defined above and G is —CN or —COOR2 wherein R2 is a C1-C4 straight or branched alkyl chain.

主权项

1. A process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein R represents one or more substituents independently selected from the group consisting of fluorine, chlorine, bromine, and iodine, said process comprising: (i) reacting a compound of formula (II): wherein X is chlorine, bromine, iodine or a triflate group (CF3SO3) or a group  wherein R is as defined above, and G is —CN or —COOR2, wherein R2 is a C1-C4 straight or branched alkyl chain, with a compound of formula (III): wherein Y is CO or SO2 in the presence of a base, with the provisos that: (a) when Y is CO, then the reaction is carried out at a temperature of 120° C. to 180° C. and the molar ratio of said compound of formula (II) to said compound of formula (III) is 1:10 to 1:30; and (b) when G is —COOR2, then Y is SO2; to obtain a compound of formula (IV): wherein X and G are as defined above; (ii) when X is chlorine, bromine, iodine or a triflate group (CF3SO3), coupling said compound of formula (IV) with a compound of formula (V): wherein R is as defined above, to obtain a compound of formula (IV) wherein X is (iii) hydrolyzing said compound of formula (IV) wherein X is obtained in (i) or (ii), to obtain said compound of formula (I); and (iv) optionally transforming said compound of formula (I) into a pharmaceutically acceptable salt thereof.