FREMGANGSMAADE TIL FREMSTILLING AF 7-SUBSTITUEREDE HEPT-6-EN- OG -HEPTANSYRER OG DERIVATER OG MELLEMPRODUKTER DERAF

摘要

A novel process for the preparation compounds of formula I wherein X is -CH2CH2- or -CH=CH-; R1 is an ester group inert to the reaction conditions; and R is an organic radical having groups which are inert under reducing conditions, by stereoselective reduction of a corresponding compound of formula II wherein R, R1 and X are as defined above and one of Z1 and Z2 is oxygen and the other is hydroxy and hydrogen, is disclosed. The compounds of formula I are pharmaceuticals, especially antiatherosclerotic, antihyperlipidemic and antihypercholesterolemic agents. The process may also be applied to the preparation of compounds of formula Iu u - OCH2 - @@CH2@@CH2 - COORu Iu wherein u is triphenylmethyl (trityl) and Ru is allyl or a radical forming an ester inert under the reaction conditions, which are intermediates in the preparation of some of the compounds of formula I. Novel processes for the preparation of earlier intermediates for use in the preparation of i.a. the compounds of formula I are also disclosed, namely process A, comprising the preparation of the compounds of formula VII (E) - OHC - CH=CH - N(R12)R13 (VII) wherein R12 is C1-3alkyl, phenyl or phenyl substituted by 1 to 3 substituents each of which is independently C1-3alkyl, C1-3alkoxy, fluoro, chloro, bromo or nitro with a maximum of two nitro groups; and R13 independently has the significance indicated above for R12, starting from corresponding compounds of formula VIII OHC - N(R12)R13 (VIII) and process B, comprising the preparation of the compounds of formula Va wherein R5 is hydrogen, C1-3alkyl, n-butyl, i-butyl, t-butyl, C3-6cycloalkyl, C1-3alkoxy, n-butoxy, i-butoxy, trifluoromethyl, fluoro, chloro, phenoxy or benzyloxy; R6 is hydrogen, C1-3alkyl, C1-3alkoxy, trifluoromethyl, fluoro, chloro, phenoxy or benzyloxy; with the provisos that not more than one of R5 and R6 is trifluoromethyl, not more than one of R5 and R6 is phenoxy, and not more than one of R5 and R6 is benzyloxy; one of R7 and R8 is phenyl trisubstituted by R9, R10 and R11 and the other is primary or secondary C1-6alkyl not containing an asymmetric carbon atom, C3-6cycloalkyl or phenyl-(CH2)m-, wherein R9 is hydrogen, C1-3alkyl, n-butyl, i-butyl, t-butyl, C1-3alkoxy, n-butoxy, i-butoxy, trifluoromethyl, fluoro, chloro, phenoxy or benzyloxy; R10 is hydrogen, C1-3alkyl, C1-3alkoxy, trifluoromethyl, fluoro, chloro, phenoxy or benzyloxy; R11 is hydrogen, C1-2alkyl, C1-2alkoxy, fluoro or chloro, and m is 1, 2 or 3; with the provisos that not more than one of R9 and R10 is trifluoromethyl, not more than one of R9 and R10 is phenoxy, and not more than one of R9 and R10 is benzyloxy, starting from a subgroup of compounds of formula VII. A specific embodiment of the above inventive concept is illustrated with the preparation of the compound of formula Ia in racemic or optically pure form; in free acid, salt, ester or delta -lactone, i.e. internal ester, form.