合成路线:The title compound was synthesized starting from the known drug CP-99,994 (I),which was subjected to catalytic hydrogenolysis of the N-(2-methoxybenzyl) group to yield (S,S)-3-amino-2-phenylpiperidine (II).Subsequent reductive alkylation of amine (II) with 2-methoxy-5-trifluoromethoxybenzaldehyde (III) in the presence of either NaBH3CN or NaBH(OAc)3 furnished the title compound.
参考文献标题:Stereoselective preparation of substd.piperidines
文献作者:Rosen,T.J.(Pfizer Inc.)
参考来源:WO 9217449
合成路线:The title compound was synthesized starting from the known drug CP-99,994 (I),which was subjected to catalytic hydrogenolysis of the N-(2-methoxybenzyl) group to yield (S,S)-3-amino-2-phenylpiperidine (II).Subsequent reductive alkylation of amine (II) with 2-methoxy-5-trifluoromethoxybenzaldehyde (III) in the presence of either NaBH3CN or NaBH(OAc)3 furnished the title compound.
合成路线:The precursor 2-methoxy-5-trifluoromethoxybenzaldehyde (III) was prepared as follows.Alkylation of 4-(trifluoromethoxy)phenol (VIII) by means of iodomethane and K2CO3 or dimethyl carbonate and DMAP furnished 4-(trifluoromethoxy)anisole (IX).Formylation of (IX) to the target aldehyde (III) was achieved by treatment with dichloromethyl methyl ether and TiCl4 or with hexamethylenetetraamine and trifluoroacetic acid.
参考文献标题:Formylation process for aromatic aldehydes
文献作者:Snyder,W.M.; Godek,D.M.; Stewart,A.M.(Pfizer Inc.)
参考来源:WO 9424081
合成路线:In an alternative procedure,the reductive alkylation of 3-amino-2-chloropyridine (IV) with 2-methoxy-5-trifluoromethoxybenzaldehyde (III) in the presence of NaBH(OAc)3 produced the 3-(benzylamino)pyridine (V).The 2-phenyl pyridine derivative (VII) was then prepared by chloride displacement with phenylmagnesium bromide (VI) in the presence of bis(triphenylphosphino)nickel(II) chloride.Catalytic hydrogenation of pyridine (VII) produced the racemic cis-piperidine,which was finally resolved into the enantiomers by using (S)-mandelic acid.
参考文献标题:Preparation of substd.piperidines
文献作者:Rosen,T.J.; Godek,D.M.; Ruggeri,S.G.; Wint,L.T.(Pfizer Inc.)
参考来源:WO 9311110
合成路线:The title compound was synthesized starting from the known drug CP-99,994 (I),which was subjected to catalytic hydrogenolysis of the N-(2-methoxybenzyl) group to yield (S,S)-3-amino-2-phenylpiperidine (II).Subsequent reductive alkylation of amine (II) with 2-methoxy-5-trifluoromethoxybenzaldehyde (III) in the presence of either NaBH3CN or NaBH(OAc)3 furnished the title compound.
参考文献标题:Synthesis and structure-activity relationships of CP-122,721,a second-generation NK-1 receptor antagonist
文献作者:Rosen,T.J.; Coffman,K.J.; McLean,S.; Crawford,R.T.; Bryce,D.K.; Gohda,Y.; Tsuchiya,M.; Nagahisa,A.; Nakane,M.; Lowe,J.A.III
参考来源:Bioorg Med Chem Lett 1998,8(3),281
产品链接: CAS No. 145742-28-5››