Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives

Process for preparing a glucopyranosyl-substituted benzyl-benzene derivative of general formula III,

• wherein
• R1 denotes C1-3-alkyl, cyclobutyl, cyclopentyl, cyclohexyl, (R)-tetrahydrofuran-3-yl, (S)-tetrahydrofuran-3-yl or tetrahydropyran-4-yl;
• and
• R2 independently of one another denote hydrogen, (C1-8-alkyl)carbonyl, (C1-8-alkyl)oxycarbonyl, phenylcarbonyl, phenyl-(C1-3-alkyl)-carbonyl, phenyl-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 or C1-6-alkyl;
• Ra, Rb, Rc independently of one another denote C1-4-alkyl, phenyl or phenyl-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 the phenyl groups mentioned in the definition of the above groups may be mono- or polysubstituted with L1;
• comprising the steps (S2), (S3) and (S4):
• (S2):
• reacting the organometallic compound of the formula VI
• wherein R1 is defined as hereinbefore and M denotes Li, Mg or MgQ, wherein Q denotes Cl, Br, I or an organic moiety;
• with a gluconolactone of general formula IV
• wherein R2 is as hereinbefore defined,
• in an organic solvent or a mixture of two or more organic solvents;
• and
• (S3):
• adding an aqueous solution comprising one or more acids such that the reaction mixture forms an aqueous phase and an organic phase whereby the organic phase has a pH in the range from about 0 to 7;
• and
• (S4):
• separating the organic phase comprising the adduct obtained in the step (S2) from the aqueous phase;
• and
• (S5):
• reacting the obtained adduct with water or an alcohol R′—OH, where R′ denotes C1-6-alkyl, or a mixture thereof in the presence of one or more acids.