BAY-27-9955
(+)-1-(4'-氟-3,5-二异丙基-6-丙基双苯-2-基)乙醇Chemical Name: (+)-1-(4'-Fluoro-3,5-diisopropyl-6-propylbiphenyl-2-yl)ethanol
CAS No. 202855-56-9
项目整合开发状态: Phase II
项目研究机构: Bayer (Originator)
合成路线:Aldol condensation between dimethyl 1,3-acetonedicarboxylate (I) and 3,5-heptanedione (II) produced dimethyl 4,6-diethyl-2-hydroxy-1,3-benzenedicarboxylate (III).After conversion of phenol (III) to the corresponding aryl triflate (IV),Suzuki coupling with 4-fluorobenzeneboronic acid (V) yielded the biphenyl derivative (VI).The diisopropyl compound (VII) was then obtained by methylation of (VI) at the benzylic position using iodomethane and LDA.Partial reduction of diester (VII) with Red-Al?gave rise to the hydroxy ester (VIII),which was further oxidized to aldehyde (IX) by treatment with pyridinium chlorochromate.Wittig reaction of aldehyde (IX) with ethyl triphenylphosphonium bromide furnished the propenyl compound (X)
合成路线:The ester group of (X) was reduced to alcohol (XI) employing LiAlH4 in boiling THF.Subsequent olefin hydrogenation in the presence of Pd/C produced the propyl compound (XII).After oxidation of the primary alcohol (XII) to aldehyde (XIII) by means of pyridinium chlorochromate,addition of methylmagnesium bromide led to the desired secondary alcohol (1,2).
📌 参考资料/链接：
参考文献标题:Substd.biphenyls
文献作者:Wolanin,D.J.; Schoen,W.R.; Kramss,R.H.; Lease,T.G.; Ladouceur,G.H.; Osterhout,M.H.; Hertzog,D.L.; Cook,J.H.II (Bayer AG; Bayer Corp.)
参考来源:US 6218431
📄 详细内容
合成路线:Aldol condensation between dimethyl 1,3-acetonedicarboxylate (I) and 3,5-heptanedione (II) produced dimethyl 4,6-diethyl-2-hydroxy-1,3-benzenedicarboxylate (III).After conversion of phenol (III) to the corresponding aryl triflate (IV),Suzuki coupling with 4-fluorobenzeneboronic acid (V) yielded the biphenyl derivative (VI).The diisopropyl compound (VII) was then obtained by methylation of (VI) at the benzylic position using iodomethane and LDA.Partial reduction of diester (VII) with Red-Al?gave rise to the hydroxy ester (VIII),which was further oxidized to aldehyde (IX) by treatment with pyridinium chlorochromate.Wittig reaction of aldehyde (IX) with ethyl triphenylphosphonium bromide furnished the propenyl compound (X)
合成路线:The ester group of (X) was reduced to alcohol (XI) employing LiAlH4 in boiling THF.Subsequent olefin hydrogenation in the presence of Pd/C produced the propyl compound (XII).After oxidation of the primary alcohol (XII) to aldehyde (XIII) by means of pyridinium chlorochromate,addition of methylmagnesium bromide led to the desired secondary alcohol (1,2).
参考文献标题:Substd.pyridines and biphenyls as anti-hypercholesterinemic,anti-hyperlipoproteinemic and anti-hyperglycemic agents
文献作者:Schmidt,G.; Wolanin,D.J.; Bischoff,H.; Schoen,W.R.; Angerbauer,R.; Schmidt,D.; Kramss,R.H.; Wohlfeil,S.; Brandes,A.; Muller-Gliemann,M.; Lease,T.G.; Ladouceur,G.H.; Osterhout,M.H.; Hertzog,D.L.; Cook,J.H.II (Bayer AG; Bayer Corp.)
参考来源:WO 9804528
产品链接: CAS No. 202855-56-9››