Intermediates for the preparation of bile acids
A method of the preparation of deoxycholic acid (DCA) or a pharmaceutically acceptable salt thereof:said method comprising: (a) hydrogenating 9-alpha-hydroxyandrost-4-en-3,17-dione (1.0) with H2to form compound (1.1); (b) reacting compound (1.1) with acid to eliminate the hydroxy group to form compo...
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creator | ACHAMPETA RATHAN PRASAD JOHN GREGORY REID ROY ARCHIBALD SWARINGEN JR ROBERT M MORIARTY AKHILA KUMAR SAHOO |
description | A method of the preparation of deoxycholic acid (DCA) or a pharmaceutically acceptable salt thereof:said method comprising: (a) hydrogenating 9-alpha-hydroxyandrost-4-en-3,17-dione (1.0) with H2to form compound (1.1); (b) reacting compound (1.1) with acid to eliminate the hydroxy group to form compound (1.2); (c) reacting diketone (1.2) with a reducing agent to form a mixture of compounds (1.3) and (1.4); (d) reacting compound (1.3) with a two carbon olefination reagent to form (Z)-3-alpha-hydroxy-5-beta-pregna-((11),17(20)-diene (1.5); (e) protecting the free hydroxyl to give (1.6); (f) reacting (1.6) with an alkylpropionate CH2CH2C(O)OR or an alkyl acrylate CH2=CHC(O)OR, wherein R is alkyl, in the presence of a Lewis acid to form (1.7); (g) hydrogenation to give (1.8); (h) reacting (1.8) with an oxidising agent to introduce a ketone at the 12-position; (i) hydrogenation to remove the 9(11) double bond and give (2.0); (j) reacting (2.0) with a reducing agent to afford the 12-hydroxy compound (2.1); and (k) deprotecting and hydrolysing (2.1) to afford DCA. Intermediates (1.1), (1.2), (1.5), (1.6), (1.7a), (1.7b), (1.9a) and (2.0a) are claimed per se. |
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Intermediates (1.1), (1.2), (1.5), (1.6), (1.7a), (1.7b), (1.9a) and (2.0a) are claimed per se.</description><language>eng</language><subject>CHEMISTRY ; METALLURGY ; ORGANIC CHEMISTRY ; STEROIDS</subject><creationdate>2011</creationdate><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20110406&DB=EPODOC&CC=GB&NR=2460350B$$EHTML$$P50$$Gepo$$Hfree_for_read</linktohtml><link.rule.ids>230,308,780,885,25564,76547</link.rule.ids><linktorsrc>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20110406&DB=EPODOC&CC=GB&NR=2460350B$$EView_record_in_European_Patent_Office$$FView_record_in_$$GEuropean_Patent_Office$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>ACHAMPETA RATHAN PRASAD</creatorcontrib><creatorcontrib>JOHN GREGORY REID</creatorcontrib><creatorcontrib>ROY ARCHIBALD SWARINGEN JR</creatorcontrib><creatorcontrib>ROBERT M MORIARTY</creatorcontrib><creatorcontrib>AKHILA KUMAR SAHOO</creatorcontrib><title>Intermediates for the preparation of bile acids</title><description>A method of the preparation of deoxycholic acid (DCA) or a pharmaceutically acceptable salt thereof:said method comprising: (a) hydrogenating 9-alpha-hydroxyandrost-4-en-3,17-dione (1.0) with H2to form compound (1.1); (b) reacting compound (1.1) with acid to eliminate the hydroxy group to form compound (1.2); (c) reacting diketone (1.2) with a reducing agent to form a mixture of compounds (1.3) and (1.4); (d) reacting compound (1.3) with a two carbon olefination reagent to form (Z)-3-alpha-hydroxy-5-beta-pregna-((11),17(20)-diene (1.5); (e) protecting the free hydroxyl to give (1.6); (f) reacting (1.6) with an alkylpropionate CH2CH2C(O)OR or an alkyl acrylate CH2=CHC(O)OR, wherein R is alkyl, in the presence of a Lewis acid to form (1.7); (g) hydrogenation to give (1.8); (h) reacting (1.8) with an oxidising agent to introduce a ketone at the 12-position; (i) hydrogenation to remove the 9(11) double bond and give (2.0); (j) reacting (2.0) with a reducing agent to afford the 12-hydroxy compound (2.1); and (k) deprotecting and hydrolysing (2.1) to afford DCA. Intermediates (1.1), (1.2), (1.5), (1.6), (1.7a), (1.7b), (1.9a) and (2.0a) are claimed per se.</description><subject>CHEMISTRY</subject><subject>METALLURGY</subject><subject>ORGANIC CHEMISTRY</subject><subject>STEROIDS</subject><fulltext>true</fulltext><rsrctype>patent</rsrctype><creationdate>2011</creationdate><recordtype>patent</recordtype><sourceid>EVB</sourceid><recordid>eNrjZND3zCtJLcpNTclMLEktVkjLL1IoyUhVKChKLUgsSizJzM9TyE9TSMrMSVVITM5MKeZhYE1LzClO5YXS3Azybq4hzh66qQX58anFBYnJqXmpJfHuTkYmZgbGpgZOxoRVAAB-qCnc</recordid><startdate>20110406</startdate><enddate>20110406</enddate><creator>ACHAMPETA RATHAN PRASAD</creator><creator>JOHN GREGORY REID</creator><creator>ROY ARCHIBALD SWARINGEN JR</creator><creator>ROBERT M MORIARTY</creator><creator>AKHILA KUMAR SAHOO</creator><scope>EVB</scope></search><sort><creationdate>20110406</creationdate><title>Intermediates for the preparation of bile acids</title><author>ACHAMPETA RATHAN PRASAD ; JOHN GREGORY REID ; ROY ARCHIBALD SWARINGEN JR ; ROBERT M MORIARTY ; AKHILA KUMAR SAHOO</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-epo_espacenet_GB2460350B3</frbrgroupid><rsrctype>patents</rsrctype><prefilter>patents</prefilter><language>eng</language><creationdate>2011</creationdate><topic>CHEMISTRY</topic><topic>METALLURGY</topic><topic>ORGANIC CHEMISTRY</topic><topic>STEROIDS</topic><toplevel>online_resources</toplevel><creatorcontrib>ACHAMPETA RATHAN PRASAD</creatorcontrib><creatorcontrib>JOHN GREGORY REID</creatorcontrib><creatorcontrib>ROY ARCHIBALD SWARINGEN JR</creatorcontrib><creatorcontrib>ROBERT M MORIARTY</creatorcontrib><creatorcontrib>AKHILA KUMAR SAHOO</creatorcontrib><collection>esp@cenet</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>ACHAMPETA RATHAN PRASAD</au><au>JOHN GREGORY REID</au><au>ROY ARCHIBALD SWARINGEN JR</au><au>ROBERT M MORIARTY</au><au>AKHILA KUMAR SAHOO</au><format>patent</format><genre>patent</genre><ristype>GEN</ristype><title>Intermediates for the preparation of bile acids</title><date>2011-04-06</date><risdate>2011</risdate><abstract>A method of the preparation of deoxycholic acid (DCA) or a pharmaceutically acceptable salt thereof:said method comprising: (a) hydrogenating 9-alpha-hydroxyandrost-4-en-3,17-dione (1.0) with H2to form compound (1.1); (b) reacting compound (1.1) with acid to eliminate the hydroxy group to form compound (1.2); (c) reacting diketone (1.2) with a reducing agent to form a mixture of compounds (1.3) and (1.4); (d) reacting compound (1.3) with a two carbon olefination reagent to form (Z)-3-alpha-hydroxy-5-beta-pregna-((11),17(20)-diene (1.5); (e) protecting the free hydroxyl to give (1.6); (f) reacting (1.6) with an alkylpropionate CH2CH2C(O)OR or an alkyl acrylate CH2=CHC(O)OR, wherein R is alkyl, in the presence of a Lewis acid to form (1.7); (g) hydrogenation to give (1.8); (h) reacting (1.8) with an oxidising agent to introduce a ketone at the 12-position; (i) hydrogenation to remove the 9(11) double bond and give (2.0); (j) reacting (2.0) with a reducing agent to afford the 12-hydroxy compound (2.1); and (k) deprotecting and hydrolysing (2.1) to afford DCA. Intermediates (1.1), (1.2), (1.5), (1.6), (1.7a), (1.7b), (1.9a) and (2.0a) are claimed per se.</abstract><oa>free_for_read</oa></addata></record> |
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title | Intermediates for the preparation of bile acids |
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