合成路线:The reaction of trifluoroacetoacetic acid ethyl ester (I) with (?)-isoborneol (II) at 130 C gives the corresponding isobornyl ester (III),which is condensed with cyclohexane-1,3-dione (IV) and 3-cyanobenzaldehyde (V) by means of ammonium acetate in refluxing ethanol to yield the octahydroquinolone (VI).The hydrolysis of the ester group of (VI),with simultaneous dehydration by means of TsOH in refluxing toluene affords 4-(3-cyanophenyl)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid (VII) as a racemic mixture.Optical resolution of (VII) through the diastereomeric salt with 1(S)-phenylethylamine (VIII) in toluene/butanol provides the desired isomer (IX),which is finally decarboxylated in N-methyl-2-pyrrolidone at 210 C to furnish the target hexahydroquinolone.
参考文献标题:Quinolone deriv.for treatment of urinary incontinence
文献作者:Warawa,J.E.; Ohnmacht,C.J.Jr.; Trainor,D.A.; Hulsizer,J.M.(AstraZeneca plc)
参考来源:EP 0755382; JP 1997512254; WO 9528388
合成路线:The condensation of 3-cyanobenzaldehyde (I) with trifluoroacetone (II) in piperidine gives 3-(4,4,4-trifluoro-3-oxo-2-butenyl)benzonitrile (III).The condensation of cyclohexane-1,3-dione (IV) with 1(R)-phenylethylamine (V) in refluxing toluene or THF yields the secondary enamine (VI),which is condensed with benzonitrile (III) by means of Tms-Cl in hot acetonitrile to afford the chiral adduct (VII).The cyclization of (VII) by means of NH3 in hot acetonitrile provides the chiral octahydroquinolone (VIII),which is finally dehydrated by means of TFA,MsOH,TsOH or HCl in refluxing acetonitrile to give the target hexahydroquinolone.
参考文献标题:Process for synthesis of alpha,beta-unsaturated ketones
文献作者:Patel,I.; Hopes,P.(AstraZeneca AB)
参考来源:WO 0210103
合成路线:The condensation of 3-cyanobenzaldehyde (I) with trifluoroacetone (II) in piperidine gives 3-(4,4,4-trifluoro-3-oxo-2-butenyl)benzonitrile (III).The condensation of cyclohexane-1,3-dione (IV) with 1(R)-phenylethylamine (V) in refluxing toluene or THF yields the secondary enamine (VI),which is condensed with benzonitrile (III) by means of Tms-Cl in hot acetonitrile to afford the chiral adduct (VII).The cyclization of (VII) by means of NH3 in hot acetonitrile provides the chiral octahydroquinolone (VIII),which is finally dehydrated by means of TFA,MsOH,TsOH or HCl in refluxing acetonitrile to give the target hexahydroquinolone.
参考文献标题:Process for asymmetric synthesis of substd.1,4-dihydropyridines
文献作者:Patel,I.; Ashworth,I.; Levin,D.(AstraZeneca AB)
参考来源:WO 0210134
合成路线:The reaction of trifluoroacetoacetic acid ethyl ester (I) with (?)-isoborneol (II) at 130 C gives the corresponding isobornyl ester (III),which is condensed with cyclohexane-1,3-dione (IV) and 3-cyanobenzaldehyde (V) by means of ammonium acetate in refluxing ethanol to yield the octahydroquinolone (VI).The hydrolysis of the ester group of (VI),with simultaneous dehydration by means of TsOH in refluxing toluene affords 4-(3-cyanophenyl)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid (VII) as a racemic mixture.Optical resolution of (VII) through the diastereomeric salt with 1(S)-phenylethylamine (VIII) in toluene/butanol provides the desired isomer (IX),which is finally decarboxylated in N-methyl-2-pyrrolidone at 210 C to furnish the target hexahydroquinolone.
参考文献标题:An asymmetric synthesis of a 4-substituted-1,4-dihydropyridine
文献作者:Ashworth,I.; Hopes,P.; Levin,D.; Patel,I.; Salloo,R.
参考来源:Tetrahedron Lett 2002,43(28),4931
产品链接: CAS No. 172649-40-0››