合成路线:The benzylation of 4-hydroxymandelic acid (I) with benzyl alcohol (II) and K2CO3 in methanol gives 4-benzyloxymandelic acid (III),which is condensed with 2-(3,4-dimethoxyphenyl)ethylamine (IV) by means of (C2H5O)2PON3 in THF to afford N-(3,4-dimethoxyphenylethyl)-4-benzyloxymandelamide (V).The reduction of (V) with diborane in THF yields the final product protected at the phenolic hydroxyl (VI) This compound is finally deprotected by hydrogenolysis with H2 over Pd/C.
合成路线:The condensation of 4-benzyloxybenzaldehyde (VII) with N-(3,4-dimethoxyphenylethyl)glycine (VIII) in refluxing pyridine also gives the protected product (VI).
合成路线:The condensation of 4-benzyloxyphenacyl chloride (XV) with the amine (IV) in refluxing CH2Cl2 gives N-(3,4-dimethoxyphenylethyl)-4-benzyloxyphenacylamine (XVI),which is reduced with NaSH4 in ethanol,also affording the protected product (VI).
合成路线:The formylation of 2-(4-hydroxyphenyl)glycine (IX) as usual gives N-formyl-2-(4-hydroxyphenyl)glycine (X),which by treatment with benzyl alcohol as before yields N-formyl-2-(4-benzyloxyphenyl)glycine (XI).The condensation of (XI) with the amine (IV) by means of butyl chloroformate affords the corresponding amide (XII),which is deformylated by treatment with HCl in methanol to give the glycinamide (XIII).The diazotation of (XIII) with NaNO2 in acetic acid affords N-(3,4-dimethoxyphenylethyl)-O-acetyl-4-benzyloxymandel-amide (XIV),which is finally reduced and deacetylated with LiAlH4 in THF yielding the protected product (VI).
合成路线:The oxidation of 4-benzyloxyphenacyl chloride (XV) with KI and DMSO gives 4-benzyloxy-alpha-oxophenylacetaldehyde (XVII),which is condensed with the amine (IV) to afford the corresponding Schiff base (XVIII).Finally,this compound is reduced with NaBH4 yielding the protected product (VI),already obtained.
合成路线:By reduction of benzyl (4-benzyloxy)phenacyl-(3,4-dimethoxyphenethyl)carbamate (XIX) with sodium prolinate-borane complex (XX) and hydrogenation over 10% palladium on a carbon catalyst.
参考文献标题:TA-064
文献作者:Blancafort,P.; Castar,J.; Serradell,M.N.
参考来源:Drugs Fut 1982,7(6),407
合成路线:A new enantioselective synthesis of R-(-)-denopamine has been published:The silylation of 4-hydroxyphenacyl chloride (I) with tert-butyldimethylchlorosilane (II) and imidazole in THF gives the silylated compound (III),which is enantioselectively reduced with borane,using the (R)-oxaazaborilidine (IV) as optically active catalyst in THF,yielding (R)-2-chloro-1-[4-(tert-butyldimethylsilyloxy)phenyl]ethanol (V).The reaction of (V) with NaI in refluxing acetone affords the corresponding iodo-alcohol (VI),which is protected with triethylchlorosilane and imidazole in DMF to give the fully silylated compound (VIII).The condensation of (VIII) with 2-(3,4-dimethoxyphenyl)ethylamine (IX) by means of triethylamine in THF at 100 C in a sealed tube yields the fully silylated denopamine (X),which is finally deprotected by a treatment with KF and HCl in methanol.
参考文献标题:A catalytic enantioselective synthesis of denopamine,a useful drug for congestive heart failure
文献作者:Link,J.O.; Corey,E.J.
参考来源:J Org Chem 1991,56(1),442
合成路线:A new enantioselective synthesis for denopamine has been reported:The acylation of 1-(4-benzyloxyphenyl)-2-[2-(3,4-dimethoxyphenyl)ethylamino]ethanone (I) with benzyloxycarbonyl chloride (II) by means of NaHCO3 in dichloromethane gives the protected aminoketone (III),which is submitted to an asymmetric reduction with (R)-(+)-2-amino-3-methyl-1,1-diphenyl-1-butanol-borane complex in THF yielding the (R)-(-)-protected alcohol (V).Finally,the debenzylation of (V) by hydrogenolysis with H2 over Pd/C in methanol affords denopamine with 96% optical purity.
参考文献标题:Asymmetric reduction of aromatic ketones.I.Enantioselective synthesis of denopamine
文献作者:Takeda,M.; Saito,K.; Kawaguchi,T.; Matsuki,K.; Iwakuma,T.
参考来源:Chem Pharm Bull 1993,41(4),639
合成路线:The benzylation of 4-hydroxymandelic acid (I) with benzyl alcohol (II) and K2CO3 in methanol gives 4-benzyloxymandelic acid (III),which is condensed with 2-(3,4-dimethoxyphenyl)ethylamine (IV) by means of (C2H5O)2PON3 in THF to afford N-(3,4-dimethoxyphenylethyl)-4-benzyloxymandelamide (V).The reduction of (V) with diborane in THF yields the final product protected at the phenolic hydroxyl (VI) This compound is finally deprotected by hydrogenolysis with H2 over Pd/C.
参考文献标题:Preparation of optically active benzyl alcohol derivative
文献作者:Noguchi,K.; Irie,K.
参考来源:JP 54070231
合成路线:The condensation of 4-benzyloxybenzaldehyde (VII) with N-(3,4-dimethoxyphenylethyl)glycine (VIII) in refluxing pyridine also gives the protected product (VI).
参考文献标题:Process for preparation of benzyl alcohol derivatives
文献作者:Ikezaki,M.; Umino,N.; Iwakuma,T.
参考来源:JP 52051333
合成路线:The formylation of 2-(4-hydroxyphenyl)glycine (IX) as usual gives N-formyl-2-(4-hydroxyphenyl)glycine (X),which by treatment with benzyl alcohol as before yields N-formyl-2-(4-benzyloxyphenyl)glycine (XI).The condensation of (XI) with the amine (IV) by means of butyl chloroformate affords the corresponding amide (XII),which is deformylated by treatment with HCl in methanol to give the glycinamide (XIII).The diazotation of (XIII) with NaNO2 in acetic acid affords N-(3,4-dimethoxyphenylethyl)-O-acetyl-4-benzyloxymandel-amide (XIV),which is finally reduced and deacetylated with LiAlH4 in THF yielding the protected product (VI).
参考文献标题:Preparation of optically active benzyl alcohol derivative
文献作者:Noguchi,K.; Irie,K.
参考来源:JP 54070232
产品链接: CAS No. 71771-90-9›› 产品链接: CAS No.64299-19-0››