# US 11,111,265 B2 · Method for preparing cholic acid compound > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,111,265 B2 - Document ID: US11111265B2 - Status: Granted - Kind: B2 - Application number: 16/759,134 - Filed: 2018-11-01 - Published: 2020-11-05 - Granted: 2021-09-07 - Earliest claimed: 2017-11-02 - Assignees: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. - Applicants: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. - Inventors: Xiquan Zhang; Xingdong Cheng; Aiming Zhang; Chunguang Xia; Lang Chen; Ce Gao - Web page: https://patentgrep.com/patent/US11111265B2 ## CPC - C07J 9/005: {containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton} - C07J 41/0094: {containing nitrile radicals, including thiocyanide radicals} - C07J 51/00: Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00 - C07J: STEROIDS (seco-steroids C07C) ## Abstract The present application relates to a method for preparing a cholic acid compound. Specifically, the method prepares a compound as shown in formula I, including subjecting a compound of formula 2 to an oxidization reaction to obtain a compound of formula 3; attaching a trimethylsilyl group to the compound of formula 3 to obtain a compound of formula 4; reacting the compound of formula 4 with acetaldehyde to obtain a compound of formula 5; subjecting the compound of formula 5 to a catalytic hydrogenation reaction to obtain a compound of formula 6; and converting a cyano group of the compound of formula 6 to a carboxyl group to give the compound of formula I. ## Claims ### Claim 1 A preparation method for a compound of formula I, comprising the following steps: a) subjecting a compound of formula 2 to an oxidization reaction in a solvent to obtain a compound of formula 3, b) attaching a protecting group to the compound of formula 3 in a solvent to obtain a compound of formula 4, c) reacting the compound of formula 4 with acetaldehyde in a solvent to obtain a compound of formula 5, d) subjecting the compound of formula 5 to a reduction reaction in a solvent under a catalyst to obtain a compound of formula 6, e) converting cyano group of the compound of formula 6 to a carboxyl group to give the compound of formula I, wherein, said R1 and R2 are each independently selected from a silyl ether protecting group. ### Claim 2 (depends on 1) The preparation method of claim 1, wherein the preparation method for the compound of formula 2 comprises the following steps: f) attaching a formyl group to a compound of formula 7 to obtain a compound of formula 8, g) converting a carboxyl group at position 23 of the compound of formula 8 to a cyano group at position 22 to obtain a compound of formula 9, and removing a formyl group from the compound of formula, 9 to obtain the compound of formula 2, ### Claim 3 (depends on 1) The preparation method of claim 1, wherein the silyl ether protecting group is selected from trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, or tert-butyldiphenylsilyl. ### Claim 4 (depends on 1) The preparation method of claim 1, wherein an oxidant used in said step a) is selected from sodium hypochlorite, bromine hypochlorite, N-bromosuccinimide, N-chlorosuccinimide, hydrogen peroxide or potassium dichromate. ### Claim 5 (depends on 4) The preparation method of claim 4, wherein in said step a, the molar ratio of the compound of formula 2 to the oxidant is selected from 1:(1 to 5). ### Claim 6 (depends on 1) The preparation method of claim 1, wherein said step a) is performed in the presence of bromine. ### Claim 7 (depends on 1) The preparation method of claim 1, wherein the solvent of said step a) is selected from dichloromethane, methanol, ethanol, propanol, diethyl ether, isopropyl ether, tetrahydrofuran, methyl tert-butyl ether, ethyl acetate, acetonitrile, acetone, or a mixed solvent thereof. ### Claim 8 (depends on 1) The preparation method of claim 1, wherein said step a) is performed in the presence of an organic acid, which is selected from formic acid, acetic acid, propionic acid, citric acid or malic acid. ### Claim 9 (depends on 1) The preparation method of claim 1, wherein said step b) is performed in the presence of an alkali metal cationic organic base, which is selected from lithium diisopropylamide, n-butyllithium, sodium diisopropylamide, potassium diisopropylamide, sodium hexamethyldisilazide, potassium hexamethyldisilazide or lithium hexamethyldisilazide. ### Claim 10 (depends on 1) The preparation method of claim 1, wherein said step b) is performed in the presence of an acid-binding agent, which is selected from triethylamine, diisopropylethylamine, tributylamine or pyridine. ### Claim 11 (depends on 1) The preparation method of claim 1, wherein said step c) is performed in the presence of boron trifluoride; aluminum trichloride, iron trichloride, zinc chloride, tin tetrachloride or niobium pentachloride. ### Claim 12 (depends on 1) The preparation method of claim 1, wherein the catalyst of said step d) is selected from Pd/C, PVC, Pt/C, Rh(OH)2, Raney Ni, or PtO2. ### Claim 13 (depends on 1) The preparation method of claim 1, wherein said step e) is performed in the presence of NaOH or KOH. ### Claim 14 (depends on 2) The preparation method of claim 2, Wherein said step f is performed in formic acid. ### Claim 15 (depends on 2) The preparation method of claim 2, wherein in said step g), the compound of formula 8 is converted to the compound of formula 9 in the presence of trifluoroacetic acid or trifluoroacetic anhydride, and sodium nitrite or potassium nitrite. ### Claim 16 (depends on 1) The preparation method of claim 1, wherein said step a) is performed in the presence of sodium bromide or potassium bromide. ### Claim 17 (depends on 1) The preparation method of claim 1 wherein the solvent of said step b) is selected from n-heptane, n-hexane, tetrahydrofuran, methyl tert-butyl ether or toluene. ### Claim 18 (depends on 1) The preparation method of claim 1, wherein the solvent of said step c) is selected from n-heptane, n-hexane, tetrahydrofuran; methyl tert-butyl ether, toluene or dichloromethane. ### Claim 19 (depends on 1) The preparation method of claim 1, wherein the solvent of said step d) is selected from methanol, ethanol, propanol or tetrahydrofuran. ### Claim 20 (depends on 2) The preparation method of claim 2, wherein in step g), a reaction of removing the formyl group from the compound of formula 9 is performed in an aqueous solution of NaOH or KOH.