新产品编号:793091
Chemical Name: 3-[4-[3,3-Bis(biphenyl-4-yl)-2-propen-1-yloxy]phenyl]-2(S)-ethoxypropionic acid
CAS No. 303110-77-2
项目整合开发状态: Preclinical
项目研究机构: Novo Nordisk (Originator)
合成路线:The Horner-Emmons condensation of 4,4'-dibromobenzophenone (I) with triethyl phosphonoacetate leads to the 3,3-diarylpropenoate (II).Ester (II) is subsequently reduced to the allylic alcohol (III) employing DIBAL in cold THF.Suzuki coupling of aryl bromide (III) with phenylboronic acid (IV) furnishes 3,3-bis-(biphenyl-4-yl)-2-propen-1-ol (V).Coupling of allylic alcohol (V) with (S) ethyl 2-ethoxy-3-(4-hydroxyphenyl)propionate (VI) by means of 1,1'-(azodicarbonyl)dipiperidine (ADDP) and tributylphosphine under Mitsunobu conditions gives rise to the ether adduct (VII).Finally,saponification of the ethyl ester group of (VII) provides the target carboxylic acid.
📌 参考资料/链接：
参考文献标题:New cpds.,their preparation and use
文献作者:Sauerberg,P.; Jeppesen,L.; Bury,P.S.; Murray,A.; Pettersson,I.(Novo Nordisk A/S)
参考来源:EP 1171414; JP 2002542218; WO 0063153
📄 详细内容
合成路线:The Horner-Emmons condensation of 4,4'-dibromobenzophenone (I) with triethyl phosphonoacetate leads to the 3,3-diarylpropenoate (II).Ester (II) is subsequently reduced to the allylic alcohol (III) employing DIBAL in cold THF.Suzuki coupling of aryl bromide (III) with phenylboronic acid (IV) furnishes 3,3-bis-(biphenyl-4-yl)-2-propen-1-ol (V).Coupling of allylic alcohol (V) with (S) ethyl 2-ethoxy-3-(4-hydroxyphenyl)propionate (VI) by means of 1,1'-(azodicarbonyl)dipiperidine (ADDP) and tributylphosphine under Mitsunobu conditions gives rise to the ether adduct (VII).Finally,saponification of the ethyl ester group of (VII) provides the target carboxylic acid.
参考文献标题:Design and synthesis of novel PPARalpha/gamma/delta triple activators using a known PPARalpha/gamma dual activator as structural template
文献作者:Mogensen,J.P.; Jeppesen,L.; Bury,P.S.; Pettersson,I.; Fleckner,J.; Nehlin,J.; Frederiksen,K.S.; Albrektsen,T.; Din,N.; Mortensen,S.B.; Svensson,L.A.; Wasserman,K.; Wulff,E.M.; Ynddal,L.; Sauerberg,P.
参考来源:Bioorg Med Chem Lett 2003,13(2),257