Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives and intermediates therein

Process for preparing the compounds of general formula III,

• wherein
• R1 denotes cyclobutyl, cyclopentyl, cyclohexyl, R-tetrahydrofuran-3-yl, S-tetrahydrofuran-3-yl or tetrahydropyran-4-yl;
• and
• R2 independently of one another denote hydrogen, (C1-18-alkyl)carbonyl, (C1-18-alkyl)oxycarbonyl, arylcarbonyl, aryl-(C1-3-alkyl)-carbonyl, aryl-C1-3-alkyl, allyl,
• RaRbRcSi, CRaRbORc, wherein two adjacent groups R2 may be linked with each other to form a bridging group SiRaRb, CRaRb or CRaORb—CRaORb;
• and
• R′ denotes hydrogen, C1-6-alkyl, (C1-4-alkyl)carbonyl, (C1-4-alkyl)oxycarbonyl, arylcarbonyl, aryl-(C1-3-alkyl)-carbonyl;
• Ra, Rb, Rc independently of one another denote C1-4-alkyl, aryl or aryl-C1-3-alkyl, while the alkyl groups may be mono- or polysubstituted by halogen;
• L1 independently of one another are selected from among fluorine, chlorine, bromine, C1-3-alkyl, C1-4-alkoxy and nitro;
• while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, which may be mono- or polysubstituted with L1;
• said method comprised of the step of adding an organometallic compound of the formula VI
• wherein R1 is defined as hereinbefore and M denotes Li or MgHal, wherein Hal denotes Cl, Br or I;
• or a derivative thereof obtained by transmetallation;
• which compound of the formula VI may be obtained by halogen-metal exchange or by the insertion of a metal in the carbon-halogen bond of a halogen-benzylbenzene compound of general formula V
• wherein R1 is defined as hereinbefore and X denotes Br or I;
• and optionally subsequent transmetallation, to a gluconolactone of general formula IV
• wherein R2 is as hereinbefore defined,
• and reacting the adduct obtained with water or an alcohol R′—OH, where R′ denotes C1-6-alkyl, in the presence of an acid and optionally the product obtained in the reaction with water wherein R′ denotes H is converted in a subsequent reaction with an acylating agent into the product of formula III wherein R′ denotes (C1-4-alkyl)carbonyl, (C1-4-alkyl)oxycarbonyl, arylcarbonyl, or aryl-(C1-3-alkyl)-carbonyl, wherein the term aryl is defined as hereinbefore.