合成路线:The condensation of 3,4-dimethylbenzyl chloride (I) with diethyl malonate (II) by means of sodium ethoxide ethanol gives the diethyl 2-(3,4-dimethylbenzyl)malonate (III),which by treatment with aqueous refluxing NaOH and the with refluxing aqueous sulfuric acid yields 3-(3,4-dimethylphenyl)propionic acid (IV).The reaction of (IV) with refluxing SOCl2 affords the corresponding acyl chloride (V),which is treated with ammonia providing the amide (VI).The reduction of (VI) with LiAlH4 in refluxing THF gives 3-(3,4-dimethylphenyl)propylamine (VII),which by condensation with 2-(4-hydroxy-3-methoxyphenyl)acetic acid (VIII) by heating at 150 C yields the corresponding amide (IX).The alkylation of the phenolic group of (IX) with 1,2-dibromoethane (X) and NaH in refluxing THF affords the 2-bromoethoxy derivative (XI),which by treatment with NaN3 and Bu4NBr in refluxing benzene gives the 2-azidoethoxy derivative (XII).Finally,this compound is reduced with H2 over Pd/C in ethyl acetate to afford the target compound.
参考文献标题:Synthesis of homovanillic amide derivatives and their analgesic activity
文献作者:Lee,J.-C.; Lee,K.-S.; Han,M.-S.; Jung,Y.S.; Choi,J.; Park,N.-S.; Ha,D.-C.; Seong,C.-M.; Lim,H.-J.; Choi,S.W.
参考来源:Arch Pharmacal Res 1996,19(3),246
合成路线:The condensation of 3,4-dimethylbenzyl chloride (I) with diethyl malonate (II) by means of sodium ethoxide ethanol gives the diethyl 2-(3,4-dimethylbenzyl)malonate (III),which by treatment with aqueous refluxing NaOH and the with refluxing aqueous sulfuric acid yields 3-(3,4-dimethylphenyl)propionic acid (IV).The reaction of (IV) with refluxing SOCl2 affords the corresponding acyl chloride (V),which is treated with ammonia providing the amide (VI).The reduction of (VI) with LiAlH4 in refluxing THF gives 3-(3,4-dimethylphenyl)propylamine (VII),which by condensation with 2-(4-hydroxy-3-methoxyphenyl)acetic acid (VIII) by heating at 150 C yields the corresponding amide (IX).The alkylation of the phenolic group of (IX) with 1,2-dibromoethane (X) and NaH in refluxing THF affords the 2-bromoethoxy derivative (XI),which by treatment with NaN3 and Bu4NBr in refluxing benzene gives the 2-azidoethoxy derivative (XII).Finally,this compound is reduced with H2 over Pd/C in ethyl acetate to afford the target compound.
参考文献标题:N-Aralkylated 4-(2-aminoethoxy)phenylacetamide derivatives as potent analgesic and antiinflammatory agents
文献作者:Lim,H.-J.; Park,N.-S.; Choi,J.-K.; Ha,D.-C.; Kim,H.-S.; Lee,B.-Y.
参考来源:Korean Journal of Medicinal Chemistry 1991,1(1),36
合成路线:The 2-chloroethylation of ethyl homovanillate (I) with 1-bromo-2-chloroethane and K2CO3 in acetone gives ethyl 2-[4-(2-chloroethoxy)-3-methoxyphenyl]acetate (II),which is treated with sodium azide in toluene followed by hydrolysis with aqueous NaOH in MeOH,yielding 2-[4-(2-azidoethoxy)-3-methoxyphenyl]acetic acid (IV).The reaction of (IV) with SOCl2 and Et3N affords the acyl chloride (V).The reaction of 3-iodo-o-xylene (VI) and acrylonitrile under the Heck reaction conditions [Pd(OAc)2,tri-o-tolylphosphine and Et3N in MeCN] gives an isomeric mixture of 3-(3,4-dimethyl-phenyl)-2-propenenitrile (VII),which is hydrogenated with Pd/C followed by Raney-Ni to provide 3-(3,4-dimethylphenyl)propylamine (IX).The coupling reaction between the acyl chloride (V) and amine (IX) with Et3N in CH2Cl2 gives the amide (X).Finally,Pd/C catalyzed hydrogenation of this compound affords 2-[4-(2-aminoethoxy)-3-methoxyphenyl]-N-[3-(3,4-dimethylphenyl)propyl]acetamide.
参考文献标题:DA-5018
文献作者:Park,N.S.; Kim,W.B.; Kim,S.H.; Seong,C.M.; Jung,Y.S.
参考来源:Drugs Fut 2000,25(11),1131
合成路线:The 2-chloroethylation of ethyl homovanillate (I) with 1-bromo-2-chloroethane and K2CO3 in acetone gives ethyl 2-[4-(2-chloroethoxy)-3-methoxyphenyl]acetate (II),which is treated with sodium azide in toluene followed by hydrolysis with aqueous NaOH in MeOH,yielding 2-[4-(2-azidoethoxy)-3-methoxyphenyl]acetic acid (IV).The reaction of (IV) with SOCl2 and Et3N affords the acyl chloride (V).The reaction of 3-iodo-o-xylene (VI) and acrylonitrile under the Heck reaction conditions [Pd(OAc)2,tri-o-tolylphosphine and Et3N in MeCN] gives an isomeric mixture of 3-(3,4-dimethyl-phenyl)-2-propenenitrile (VII),which is hydrogenated with Pd/C followed by Raney-Ni to provide 3-(3,4-dimethylphenyl)propylamine (IX).The coupling reaction between the acyl chloride (V) and amine (IX) with Et3N in CH2Cl2 gives the amide (X).Finally,Pd/C catalyzed hydrogenation of this compound affords 2-[4-(2-aminoethoxy)-3-methoxyphenyl]-N-[3-(3,4-dimethylphenyl)propyl]acetamide.
参考文献标题:Synthesis of 3-arylpropylamine derivatives from aryl halides using Heck reaction
文献作者:Lee,C.W.; Park,N.S.; Seong,C.M.; Jung,Y.S.; Baek,G.H.; Cho,S.J.
参考来源:Bull Korean Chem Soc 1999,20232-236
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