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PROCESS FOR PREPARATION OF OBETICHOLIC ACID

IP.com Disclosure Number: IPCOM000246393D
Publication Date: 2016-Jun-03
Document File: 3 page(s) / 43K

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Abstract

Three different processes for the preparation of obeticholic acid

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PROCESS FOR PREPARATION OF OBETICHOLIC ACID

Three different processes for the preparation of obeticholic acid are reported here.

Process I

In this process, chenodeoxycholic acid (CDCA) is oxidized in presence of sodium hypochlorite to provide compound of formula (I). Compound of formula (I) is esterified in acidic condition to provide compound of formula (II). The 3-hydroxy group of compound of formula (II) is protected by an acetyl group to provide compound of formula (III). The free 7-hydroxy group of compound of formula (III) is silylated in presence of sodium iodide and triethylamine to provide compound of formula (IV). The compound of formula (IV) is reacted with acetaldehyde in presence of a Lewis acid to provide compound of formula (V), which is hydrogenated in presence of palladium-charcoal to provide compound of formula (VI). The compound of formula (VI) is epimerized by an organic base like 1,8-diazabicyclo[5.4.0]undec-7- ene (DBU) to provide compound of formula (VII). The compound of formula (VII) is de-acetylated in acidic condition to provide compound of formula (VIII). The 7-keto group of compound of formula (VIII) is reduced in presence of sodium borohydride to provide compound of formula (IX), which is hydrolyzed to provide obeticholic acid (X).

Process II

In this process, the free 3-hydroxy group of compound of formula (II) is silylated with trimethyl silylchloride to provide compound of formula (IIIA). The free 7- hydroxy group of compound of f...