合成路线:1) The optical resolution of pipecolic acid (I) with (+)-tartaric acid in water-ethanol gives L-pipecolic acid (II),which by reaction with Cl5P in acetyl chloride is converted to the acyl chloride (III).The condensation of (III) with 2,6-xylidine (IV) by means of N-methylpyrrolidone (NMP) in acetone affords L-pipecolic acid 2,6-xylidide (V),which is finally alkylated with propyl bromide (VI) and K2CO3 in hot isopropanol.
合成路线:2) The protection of L-pipecolic acid (II) with benzyl chloroformate (VII) gives the benzyloxycarbonyl compound (VIII),which is condensed with o-toluidine (IX) by means of SOCl2 and dimethylaminopyridine (DMAP) yielding the amide (X).The methylation of (X) with methyl iodide and palladium diacetate in acetic acid affords the 2,6-xylidide (XI),which is deprotected with HBr in acetic acid to give L-pipecolic acid 2,6-xylidide (V).Finally,this compound is alkylated with propyl iodide and K2CO3 in acetonitrile.
合成路线:3) The protection of 1,2,3,6-tetrahydropyridine-2(S)-carboxylic acid (XII) with benzyl chloroformate (VII) gives the benzyloxycarbonyl derivative (XIII),which is condensed with 2,6-xylidine (IV) with SOCl2 and DMAP as before yielding the amide (XIV).Deprotection of (XIV) with iodotrimethylsilane in dichloromethane affords N-(2,6-dimethylphenyl)-1,2,3,6-tetrahydropyridine-2(S)-carboxamide (XV),which is reduced with H2 over Rh/Al2O3 in DMF giving the saturated amide (V).Finally,this compound is alkylated with propyl iodide and K2CO3 as before.
参考文献标题:ROPIVACAINE HYDROCHLORIDE < Rec INNM >
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1989,14(8),767
合成路线:2) The protection of L-pipecolic acid (II) with benzyl chloroformate (VII) gives the benzyloxycarbonyl compound (VIII),which is condensed with o-toluidine (IX) by means of SOCl2 and dimethylaminopyridine (DMAP) yielding the amide (X).The methylation of (X) with methyl iodide and palladium diacetate in acetic acid affords the 2,6-xylidide (XI),which is deprotected with HBr in acetic acid to give L-pipecolic acid 2,6-xylidide (V).Finally,this compound is alkylated with propyl iodide and K2CO3 in acetonitrile.
参考文献标题:Synthesis of carbon-14 labelled ropivacaine,a local anaesthetic agent
文献作者:Sahlberg,C.
参考来源:J Label Compd Radiopharm 1987,24(5),529
合成路线:3) The protection of 1,2,3,6-tetrahydropyridine-2(S)-carboxylic acid (XII) with benzyl chloroformate (VII) gives the benzyloxycarbonyl derivative (XIII),which is condensed with 2,6-xylidine (IV) with SOCl2 and DMAP as before yielding the amide (XIV).Deprotection of (XIV) with iodotrimethylsilane in dichloromethane affords N-(2,6-dimethylphenyl)-1,2,3,6-tetrahydropyridine-2(S)-carboxamide (XV),which is reduced with H2 over Rh/Al2O3 in DMF giving the saturated amide (V).Finally,this compound is alkylated with propyl iodide and K2CO3 as before.
参考文献标题:Synthesis of tritium labelled ropivacaine - A new potential local anaesthetic
文献作者:Gawell,L.
参考来源:J Label Compd Radiopharm 1987,24(5),521
产品链接: CAS No. 84057-95-4››