合成路线:The enantioselective synthesis of the (R)-enantiomer of rolipram,which is the most active,has been published:The reaction of 3-benzyloxy-4-methoxybenzaldehyde (I) with nitromethane by means of ammonium acetate in refluxing acetic acid gives 3-benzyloxy-4-methoxy-beta-nitrostyrene (II),which is condensed with the chiral oxazolidinone (R)-3-acetyl-4-benzyl-2-oxazolidinone (III) by means of sodium bis(trimethylsilyl)amine in THF yielding 4(R)-benzyl-3-[3(R)-(3-benzyloxy-4-methoxyphenyl)-4-nitrobutyryl]-2-oxa zolidinone (IV).Hydrogenation of (IV) with H2 over Raney Ni in ethanol - ethyl acetate affords 4(R)-(3-hydroxy-4-methoxyphenyl)-2-pyrrolidinone (VI) through the intermediate benzyl ether (V).Finally,compound (VI) is etherified with cyclopentyl bromide (VII) by means of NaH in refluxing THF.
参考文献标题:Enantioselective synthesis of the antidepressant rolipram by Michael addition to a nitroolefin
文献作者:Schmiechen,R.; Mulzer,J.; Zuhse,R.
参考来源:Angew Chem.Int Ed Engl 1992,31(7),870
合成路线:A new synthesis for (-)-(R)-rolipram has been described:The cyclization of (S)-2-hydroxy-1-phenylethylamine (I) with 3-formylpropionic acid (II),or the reductocyclization of N-[2-hydroxy-1(S)-phenylethyl]succinimide (III) with NaBH4,yields the bicyclic amine (IV),which is treated with benzyl chloroformate and phenylselenyl bromide to afford the bicyclic ketoester (V).The stereocontrolled arylation of (V) with 4-bromo-2-(cyclopentyloxy)anisole by means of tert-butyllithium in THF gives the arylated ketoester (VII),which is decarboxylated with ammonium formate and Pd/C in methanol to the bicyclic pyrrolidone (VIII).The ring cleavage of (VIII) with Ca metal in liquid ammonia affords the hydroxypyrrolidone (IX),which is finally reduced with sodium cyanoborohydride in THF-methanol.
参考文献标题:The synthesis of aracemic 4-substituted pyrrolidinones and 3-substituted pyrrolidines.An asymmetric synthesis of (-)-rolipram
文献作者:Meyers,A.I.; Snyder,L.
参考来源:J Org Chem 1993,58(1),36
合成路线:This compound can be obtained by three related ways:1) The condensation of 3-cyclopentyloxy-4-methoxybenzaldehyde (I) with diethyl malonate (II) by means of piperidine in refluxing acetic acid gives diethyl 3-cyclopentyloxy-4-methoxybenzylidenemalonate (III),which is treated with nitromethane and tetramethylguanidine (TMG) yielding diethyl 2-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-nitroethyl]malonate (IV).The reductocyclization of (IV) with H2 over Raney Ni in hot methanol gives ethyl 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopyrrolidine-3-carboxylat (V).Finally,this compound is hydrolyzed and decarboxylated.2) The reaction of malonate (III) with KCN in ethanol at 60 C gives ethyl 3-cyano-3-(3-cyclopentyloxy-4-methoxyphenyl)propionate (VI),which is reduced with H2 over PtO2 in acetic acid yielding ethyl 4-amino-3-(3-cyclopentyloxy-4-methoxyphenyl)butanoate (VII).Finally,this compound is hydrolyzed and cyclized.3) The reaction of malonate (III) with KNC in refluxing ethanol gives 3-cyano-3-(3-cyclopentyloxy-4-methoxy)propanoic acid (VIII),which is reduced with H2 over PtO2 as before yielding 4-amino-3-(3-cyclopentyloxy-4-methoxyphenyl)butanoic acid (IX).Finally,this compound is cyclized.
参考文献标题:4-(Polyalkoxyphenyl)-2-pyrrolidones (II).
文献作者:Huth,A.; Schmiechen,R.; Kehr,W.; Palenschat,D.; Paschelke,G.; Wachtel,H.(Schering AG)
参考来源:BE 846335; ES 451518; FR 2324299; GB 1563398; US 4153713
产品链接: CAS No. 61413-54-5››