Patent ID: 7994352

Claim:
A process for preparing 3α,7α(β)-dihydroxy-6α(β)-alkyl-5β-cholanic acids with general formula (I) wherein the dashed bond (—) in position 6 and 7 indicates that the substituent may be in position α or β, chosen in the class consisting of: i) 3α,7α-dihydroxy-6α-alkyl-5β-cholanic acid with general formula (IA) ii) 3α,7α-dihydroxy-6β-alkyl-5β-cholanic acid with general formula (IB) iii) 3α,7β-dihydroxy-6α-alkyl-5β-cholanic acid with general formula (IC) wherein R is a linear or branched C 1 -C 5 alkyl, wherein said process comprises: a) esterifying 3α-hydroxy-7-keto-5β-cholanic acid (II) in methanol in an acidic environment to obtain methyl 3α-hydroxy-7-keto-5β-cholanate (III), b) silylating methyl 3α-hydroxy-7-keto-5β-cholanate (III) with trimethylchlorosilane to obtain the corresponding methyl 3α-trimethylsiloxy-7-keto-5β-cholanate (IV), c) silylating methyl 3α-trimethylsiloxy-7-keto-5β-cholanate (IV) in the presence of a strong base and trimethylchlorosilane to obtain methyl 3α,7-di-trimethylsiloxy-6-en-5β-cholanate (V), d) reacting methyl 3α,7-di-trimethylsiloxy-6-en-5β-cholanate (V) with the aldehyde R—CHO and a Lewis acid, wherein R is a linear or branched C 1 -C 5 alkyl, to obtain methyl 3α-hydroxy-6-alkylidene-7-keto-5β-cholanate (VI), e) hydrolysing methyl 3α-hydroxy-6-alkylidene-7-keto-5β-cholanate (VI) to 3α-hydroxy-6-alkylidene-7-keto-5β-cholanic acid (VII), f) hydrogenating 3α-hydroxy-6-alkylidene-7-keto-5β-cholanic acid (VII) in an aqueous alkaline environment with Pd/C to 3α-hydroxy-6β-alkyl-7-keto-5β-cholanic acid (VIII) g) optionally heat treating the intermediate (VIII) in an aqueous alkaline environment to obtain the corresponding 3α-hydroxy-6α-alkyl-7-keto-5β-cholanic acid (IX) h) reducing the ketonic group in position (7) to 7-hydroxy group of the intermediate (VIII) or (IX) according to one of the following alternative operating conditions: h′) reducing 3α-hydroxy-6α-alkyl-7-keto-5β-cholanic acid (IX) with metallic hydride to obtain 3α,7α-dihydroxy-6α-alkyl-5β-cholanic acid (IA), h″) reducing 3α-hydroxy-6α-alkyl-7-keto-5β-cholanic acid (IX) with metallic sodium and alcohol to obtain 3α,7β-dihydroxy-6α-alkyl-5β-cholanic acid (IC); h′″) reducing 3α-hydroxy-6β-alkyl-7-keto-5β-cholanic acid (VIII) with metallic hydride to obtain 3α,7α-dihydroxy-6β-alkyl-5β-cholanic acid (IB).