(R)-2-(2,5-difluorophenyl)pyrrolidine, preparation method and applications thereof
The invention discloses (R)-2-(2,5-difluorophenyl)pyrrolidine, a preparation method and applications thereof. The preparation method comprises: carrying out a hydrogenation reduction reaction on 5-(2,5-difluorophenyl)-3,4-dihydro-2H-pyrrole in the presence of imine reductase and reduced coenzyme NAD...
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| creator | CHENG ZHANBING JIAO QI XIAO YU TIAN ZHENHUA DING SHAONAN WANG MEINI WANG SHU |
| description | The invention discloses (R)-2-(2,5-difluorophenyl)pyrrolidine, a preparation method and applications thereof. The preparation method comprises: carrying out a hydrogenation reduction reaction on 5-(2,5-difluorophenyl)-3,4-dihydro-2H-pyrrole in the presence of imine reductase and reduced coenzyme NADPH to obtain the product. According to the invention, the ee value of the prepared (R)-2-(2,5-difluorophenyl)pyrrolidine can at least reach 94%, and the conversion rate can at least reach 84% through HPLC detection; the industrial production requirements of (R)-2-(2,5-difluorophenyl)pyrrolidine andlarotrectinib are met; and compared with the chemical method, the preparation method of the invention is low in cost and environment-friendly.
本发明公开了一种(R)-2-(2,5-二氟苯基)吡咯烷及其制备方法和应用。所述的制备方法包括：在亚胺还原酶和还原型辅酶NADPH的存在下，将5-(2,5-二氟苯基)-3,4-二氢-2H-吡咯进行加氢还原反应，即可。利用本发明的制备方法制备得到的R型的2-(2,5-二氟苯基)吡咯烷，ee值至少可达94％，通过HPLC检测转化率至少可达84％；满足了(R)-2-(2,5-二氟苯基)吡咯烷和larotrectinib的工业化生产需求；且本发明制备方法比化学方法成本更低，环境更加友好。 |
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本发明公开了一种(R)-2-(2,5-二氟苯基)吡咯烷及其制备方法和应用。所述的制备方法包括：在亚胺还原酶和还原型辅酶NADPH的存在下，将5-(2,5-二氟苯基)-3,4-二氢-2H-吡咯进行加氢还原反应，即可。利用本发明的制备方法制备得到的R型的2-(2,5-二氟苯基)吡咯烷，ee值至少可达94％，通过HPLC检测转化率至少可达84％；满足了(R)-2-(2,5-二氟苯基)吡咯烷和larotrectinib的工业化生产需求；且本发明制备方法比化学方法成本更低，环境更加友好。</description><language>chi ; eng</language><subject>BEER ; BIOCHEMISTRY ; CHEMISTRY ; COMPOSITIONS THEREOF ; CULTURE MEDIA ; ENZYMOLOGY ; FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE ; HETEROCYCLIC COMPOUNDS ; METALLURGY ; MICROBIOLOGY ; MICROORGANISMS OR ENZYMES ; MUTATION OR GENETIC ENGINEERING ; ORGANIC CHEMISTRY ; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS ; SPIRITS ; VINEGAR ; WINE</subject><creationdate>2020</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=20200424&DB=EPODOC&CC=CN&NR=111057729A$$EHTML$$P50$$Gepo$$Hfree_for_read</linktohtml><link.rule.ids>230,308,776,881,25542,76290</link.rule.ids><linktorsrc>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20200424&DB=EPODOC&CC=CN&NR=111057729A$$EView_record_in_European_Patent_Office$$FView_record_in_$$GEuropean_Patent_Office$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>CHENG ZHANBING</creatorcontrib><creatorcontrib>JIAO QI</creatorcontrib><creatorcontrib>XIAO YU</creatorcontrib><creatorcontrib>TIAN ZHENHUA</creatorcontrib><creatorcontrib>DING SHAONAN</creatorcontrib><creatorcontrib>WANG MEINI</creatorcontrib><creatorcontrib>WANG SHU</creatorcontrib><title>(R)-2-(2,5-difluorophenyl)pyrrolidine, preparation method and applications thereof</title><description>The invention discloses (R)-2-(2,5-difluorophenyl)pyrrolidine, a preparation method and applications thereof. The preparation method comprises: carrying out a hydrogenation reduction reaction on 5-(2,5-difluorophenyl)-3,4-dihydro-2H-pyrrole in the presence of imine reductase and reduced coenzyme NADPH to obtain the product. According to the invention, the ee value of the prepared (R)-2-(2,5-difluorophenyl)pyrrolidine can at least reach 94%, and the conversion rate can at least reach 84% through HPLC detection; the industrial production requirements of (R)-2-(2,5-difluorophenyl)pyrrolidine andlarotrectinib are met; and compared with the chemical method, the preparation method of the invention is low in cost and environment-friendly.
本发明公开了一种(R)-2-(2,5-二氟苯基)吡咯烷及其制备方法和应用。所述的制备方法包括：在亚胺还原酶和还原型辅酶NADPH的存在下，将5-(2,5-二氟苯基)-3,4-二氢-2H-吡咯进行加氢还原反应，即可。利用本发明的制备方法制备得到的R型的2-(2,5-二氟苯基)吡咯烷，ee值至少可达94％，通过HPLC检测转化率至少可达84％；满足了(R)-2-(2,5-二氟苯基)吡咯烷和larotrectinib的工业化生产需求；且本发明制备方法比化学方法成本更低，环境更加友好。</description><subject>BEER</subject><subject>BIOCHEMISTRY</subject><subject>CHEMISTRY</subject><subject>COMPOSITIONS THEREOF</subject><subject>CULTURE MEDIA</subject><subject>ENZYMOLOGY</subject><subject>FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE</subject><subject>HETEROCYCLIC COMPOUNDS</subject><subject>METALLURGY</subject><subject>MICROBIOLOGY</subject><subject>MICROORGANISMS OR ENZYMES</subject><subject>MUTATION OR GENETIC ENGINEERING</subject><subject>ORGANIC CHEMISTRY</subject><subject>PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS</subject><subject>SPIRITS</subject><subject>VINEGAR</subject><subject>WINE</subject><fulltext>true</fulltext><rsrctype>patent</rsrctype><creationdate>2020</creationdate><recordtype>patent</recordtype><sourceid>EVB</sourceid><recordid>eNrjZAjSCNLUNdLVMNIx1U3JTMspzS_KL8hIzavM0SyoLCrKz8lMycxL1VEoKEotSCxKLMnMz1PITS3JyE9RSMwD4oKCnMxksHCxQklGalFqfhoPA2taYk5xKi-U5mZQdHMNcfbQTS3Ij08tLkhMTs1LLYl39jM0NDQwNTc3snQ0JkYNAGpENzk</recordid><startdate>20200424</startdate><enddate>20200424</enddate><creator>CHENG ZHANBING</creator><creator>JIAO QI</creator><creator>XIAO YU</creator><creator>TIAN ZHENHUA</creator><creator>DING SHAONAN</creator><creator>WANG MEINI</creator><creator>WANG SHU</creator><scope>EVB</scope></search><sort><creationdate>20200424</creationdate><title>(R)-2-(2,5-difluorophenyl)pyrrolidine, preparation method and applications thereof</title><author>CHENG ZHANBING ; JIAO QI ; XIAO YU ; TIAN ZHENHUA ; DING SHAONAN ; WANG MEINI ; WANG SHU</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-epo_espacenet_CN111057729A3</frbrgroupid><rsrctype>patents</rsrctype><prefilter>patents</prefilter><language>chi ; eng</language><creationdate>2020</creationdate><topic>BEER</topic><topic>BIOCHEMISTRY</topic><topic>CHEMISTRY</topic><topic>COMPOSITIONS THEREOF</topic><topic>CULTURE MEDIA</topic><topic>ENZYMOLOGY</topic><topic>FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE</topic><topic>HETEROCYCLIC COMPOUNDS</topic><topic>METALLURGY</topic><topic>MICROBIOLOGY</topic><topic>MICROORGANISMS OR ENZYMES</topic><topic>MUTATION OR GENETIC ENGINEERING</topic><topic>ORGANIC CHEMISTRY</topic><topic>PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS</topic><topic>SPIRITS</topic><topic>VINEGAR</topic><topic>WINE</topic><toplevel>online_resources</toplevel><creatorcontrib>CHENG ZHANBING</creatorcontrib><creatorcontrib>JIAO QI</creatorcontrib><creatorcontrib>XIAO YU</creatorcontrib><creatorcontrib>TIAN ZHENHUA</creatorcontrib><creatorcontrib>DING SHAONAN</creatorcontrib><creatorcontrib>WANG MEINI</creatorcontrib><creatorcontrib>WANG SHU</creatorcontrib><collection>esp@cenet</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>CHENG ZHANBING</au><au>JIAO QI</au><au>XIAO YU</au><au>TIAN ZHENHUA</au><au>DING SHAONAN</au><au>WANG MEINI</au><au>WANG SHU</au><format>patent</format><genre>patent</genre><ristype>GEN</ristype><title>(R)-2-(2,5-difluorophenyl)pyrrolidine, preparation method and applications thereof</title><date>2020-04-24</date><risdate>2020</risdate><abstract>The invention discloses (R)-2-(2,5-difluorophenyl)pyrrolidine, a preparation method and applications thereof. The preparation method comprises: carrying out a hydrogenation reduction reaction on 5-(2,5-difluorophenyl)-3,4-dihydro-2H-pyrrole in the presence of imine reductase and reduced coenzyme NADPH to obtain the product. According to the invention, the ee value of the prepared (R)-2-(2,5-difluorophenyl)pyrrolidine can at least reach 94%, and the conversion rate can at least reach 84% through HPLC detection; the industrial production requirements of (R)-2-(2,5-difluorophenyl)pyrrolidine andlarotrectinib are met; and compared with the chemical method, the preparation method of the invention is low in cost and environment-friendly.
本发明公开了一种(R)-2-(2,5-二氟苯基)吡咯烷及其制备方法和应用。所述的制备方法包括：在亚胺还原酶和还原型辅酶NADPH的存在下，将5-(2,5-二氟苯基)-3,4-二氢-2H-吡咯进行加氢还原反应，即可。利用本发明的制备方法制备得到的R型的2-(2,5-二氟苯基)吡咯烷，ee值至少可达94％，通过HPLC检测转化率至少可达84％；满足了(R)-2-(2,5-二氟苯基)吡咯烷和larotrectinib的工业化生产需求；且本发明制备方法比化学方法成本更低，环境更加友好。</abstract><oa>free_for_read</oa></addata></record> |
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| subjects | BEER BIOCHEMISTRY CHEMISTRY COMPOSITIONS THEREOF CULTURE MEDIA ENZYMOLOGY FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE HETEROCYCLIC COMPOUNDS METALLURGY MICROBIOLOGY MICROORGANISMS OR ENZYMES MUTATION OR GENETIC ENGINEERING ORGANIC CHEMISTRY PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS SPIRITS VINEGAR WINE |
| title | (R)-2-(2,5-difluorophenyl)pyrrolidine, preparation method and applications thereof |
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