合成路线:An alternative procedure involves hydrolysis of racemic ethyl 2-(2-oxopyrrolidin-1-yl)burytate (VI) with sodium hydroxide to give racemic 2-(2-oxopyrrolidin-1-yl)butyric acid (VII),which is resolved by fractional crystallization with (R)-(+)-alpha-methylbenzylamine in benzene,followed by acid-base treatment to give (S)-2-(2-oxopyrrolidin-1-yl)butyric acid (VIII).Compound (VIII) is finally treated with ethyl chloroformiate and ammonia in dichloromethane.
合成路线:A third procedure involves Ni-Raney desulfurization of (S)-4-(methylthio)-2-(2-oxopirrolidin-1-yl)butyramide (XI),prepared from (S)-2-amino-4-(methylthio)butyramide (IX) by reacttion with 4-chlorobutyryl chloride (IV).Compound (XI) can also be obtained by treatment of (IX) with ethyl 4-bromobutyrate (II) to give ethyl (S)-4-[1-(carbamoyl)-3-(methythio)propylamino]butyrate (X),which is cyclized in toluene by means of 2-hydroxypyridine.
合成路线:Reaction of (S)-2-aminobutyramide (I) with ethyl 4-bromobutyrate (II) in the presence of triethylamine in toluene gives ethyl (S)-4-[1-(carbamoyl)propylamino]butyrate (III),which is cyclized in toluene by means of 2-hydroxypyridine.Compound (I) can also be condensed with 4-chlorobutyryl chloride (IV) either directly in the presence of tetrabutylammonium bromide (TBAB) in dichloromethane,followed by in situ treatment with potassium hydroxide,or via the isolation of intermediate (S)-N-[1-(carbamoyl)propyl]-4-chlorobutyramide (V).An alternative procedure involves hydrolysis of racemic ethyl 2-(2-oxopyrrolidin-1-yl)butyrate (VI) with sodium hydroxide to give racemic 2-(2-oxopyrrolidin-1-yl)butyric acid (VII),which is resolved by fractional crystallization with (R)-(+)-alpha-methylbenzylamine in benzene,followed by acid-base treatment to give (S)-2-(2-oxopyrrolidin-1-yl)butyric acid (VIII).Compound (VIII) is finally treated with ethyl chloroformiate and ammonia in dichloromethane.A third procedure involves Ni-Raney desulfurization of (S)-4-(methylthio)-2-(2-oxopyrrolidin-1-yl)butyramide (XI),prepared from (S)-2-amino-4-(methylthio)butyramide (IX) by reaction with 4-chlorobutyryl chloride (IV).Compound (XI) can also be obtained by treatment of (IX) with ethyl 4-bromobutyrate (II) to give ethyl (S)-4-[1-(carbamoyl)-3-(methylthio)propylamino]butyrate (X),which is cyclized in toluene by means of 2-hydroxypyridine.
参考文献标题:The preparation of S-alpha-ethyl-2-oxo-1-pyrrolidineacetamide
文献作者:Cossement,E.; Motte,G.; Geerts,J.-P.; Gobert,J.(UCB SA)
参考来源:GB 2225322
合成路线:The condensation of 2-pyrrolidone (I) with ethyl 2-bromobutyrate (II) by means of NaOEt in ethanol gives 2-(2-oxopyrrolidin-1-yl)butyric acid ethyl ester (III),which is hydrolyzed with NaOH to the corresponding acid (IV).The reaction of (IV) with SOCl2 affords the acyl chloride (V),which is treated with ammonia to provide the expected amide (VI).Alternatively,the reaction of acid (IV) with ammonia and thermolysis of the resulting ammonium salt also gives the butyramide (VI).Finally,the optical resolution of the racemic amide (VI) is performed by chiral HPLC.
合成路线:The condensation of pyrrolidin-2-one (I) with ethyl 2-bromobutyrate (II) by means of NaH or sodium ethoxide gives ethyl 2-(2-oxopyrrolidino)butyrate (III),which is then treated with NH3 in methanol.
参考文献标题:New N-substd.lactams
文献作者:Strubbe,J.H.L.; Linz,R.A.(UCB SA)
参考来源:DE 2106418
合成路线:The condensation of 2-pyrrolidone (I) with 2-oxobutyric acid (II) in refluxing toluene gives 2-(2-oxopyrrolidin-1-yl)-2-butenoic acid (III),which is treated with PCl5 in THF to yield the acyl chloride (IV).The reaction of (IV) with dry ammonia affords the corresponding amide (V),which is finally submitted to an asymmetric hydrogenation with H2 over a chiral Rh catalyst to provide the desired chiral butyramide.
合成路线:Reductive amination of 5-hydroxy-4-propyl-2-furanone (I) with (S)-2-aminobutyramide (II) in the presence of NaBH4 yields the dihydropyrrolone (III).Transfer hydrogenation of (III) with ammonium formate and Pd/C provides a diastereoisomeric mixture of pyrrolidinones,from which the title compound is isolated by preparative HPLC on chiral phase.
参考文献标题:2-Oxo-1-pyrrolidine derivs.,processes for preparing them and their uses
文献作者:Michel,P.; Differding,E.; Pasau,P.; Kenda,B.; Lallemand,B.; Matagne,A.; Talaga,P.(UCB SA)
参考来源:WO 0162726; WO 0164637
合成路线:The condensation of 2-pyrrolidone (I) with ethyl 2-bromobutyrate (II) by means of NaOEt in ethanol gives 2-(2-oxopyrrolidin-1-yl)butyric acid ethyl ester (III),which is hydrolyzed with NaOH to the corresponding acid (IV).The reaction of (IV) with SOCl2 affords the acyl chloride (V),which is treated with ammonia to provide the expected amide (VI).Alternatively,the reaction of acid (IV) with ammonia and thermolysis of the resulting ammonium salt also gives the butyramide (VI).Finally,the optical resolution of the racemic amide (VI) is performed by chiral HPLC.
参考文献标题:Process for preparing (S)- and (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide
文献作者:Cavoy,E.; Hamende,M.; Deleers,M.; Canvat,J.-P.; Zimmermann,V.(UCB SA)
参考来源:US 6124473
合成路线:The condensation of 2-pyrrolidone (I) with ethyl 2-bromobutyrate (II) by means of NaOEt in ethanol gives 2-(2-oxopyrrolidin-1-yl)butyric acid ethyl ester (III),which is hydrolyzed with NaOH to the corresponding acid (IV).The reaction of (IV) with SOCl2 affords the acyl chloride (V),which is treated with ammonia to provide the expected amide (VI).Alternatively,the reaction of acid (IV) with ammonia and thermolysis of the resulting ammonium salt also gives the butyramide (VI).Finally,the optical resolution of the racemic amide (VI) is performed by chiral HPLC.
参考文献标题:Process for the preparation of levetiracetam
文献作者:Cavoy,E.; Hamende,M.; Deleers,M.; Canvat,J.-P.; Zimmermann,V.; Futagawa,T.(Daicel Chemical Industries,Ltd.; UCB SA)
参考来源:US 6107492
合成路线:The condensation of 2-pyrrolidinone (I) with 2-oxoacetic acid (II) in ethyl ether gives 2-hydroxy-2-(2-oxopyrrolidin-1-yl)acetic acid (III),which is fully methylated with methanol and conc.sulfuric acid to yield 2-methoxy-2-(2-oxopyrrolidin-1-yl)acetic acid methyl ester (IV).The reaction of (IV) with PCl3 in hot toluene affords 2-chloro-2-(2-oxopyrrolidin-1-yl)acetic acid methyl ester (V),which is condensed with triethyl phosphite (VI),also in hot toluene,to provide the dimethyl phosphonate (VII).The condensation of (VII) with acetaldehyde (VIII) in THF by means of tetramethylguanidine gives 2-(2-oxopyrrolidin-1-yl)-2-butenoic acid methyl ester (IX),which is reduced with H2 and a chiral Rhodium catalyst in THF to yield 2(S)-(2-oxopyrrolidin-1-yl)butyric acid methyl ester (X).Finally,this ester is treated with ammonia in methanol to afford the target chiral amide.
参考文献标题:Highly enantiomerically pure lactam-substd.propanoic acid derivs.and methods of making and using same
文献作者:Boaz,N.W.; Debenham,S.D.
参考来源:WO 0226705
产品链接: CAS No. 102767-28-2››