合成路线:In an alternative procedure,the intermediate amino tetraacetate (I) is acylated by chloroacetyl chloride (II),yielding chloroacetamide (III).The amide N is then alkylated with bromoethyl acetate (IV) to produce (V).Simultaneous hydrolysis of the acetate esters and the chloro group in aqueous sulfuric acid furnishes the title compound.
合成路线:Similarly,the tetrahydroxy amine (I) is acylated by chloroacetyl chloride (II) to produce the tetraester amide (III).After amide alkylation with bromoethyl acetate (IV),the resultant penta-ester (V) is hydrolyzed to the title compound using aqueous sulfuric acid.
参考文献标题:Synthesis of ioversol using chloroacetyl chloride
文献作者:McCarthy,W.Z.; Kneller,M.T.; Lin,Y.; White,D.H.(Mallinckrodt Medical Inc.)
参考来源:WO 9301840
合成路线:Chlorination of 5-amino-2,4,6-triiodoisophthalic acid (I) with SOCl2 in EtOAc or toluene affords acid chloride (II).Yields have been improved with the addition of benzyltriethylammonium chloride as a catalyst.Acid chloride (II) is then condensed with 3-amino-1,2-propanediol (III) to produce diamide (IV).Compound (IV) is converted to the tetraacetate ester (V) employing acetic anhydride in pyridine.Subsequent acylation of the amino group of (V) with acetoxyacetyl chloride (VI) gives amide (VII).After saponification of the ester groups of (VII),the resultant hydroxy acetamide (VIII) is alkylated by 2-chloroethanol (IX) to furnish the title compound.Alternatively,amide (VIII) is alkylated by bromoethyl acetate (X),producing (XI).Hexa-ester (XI) is finally hydrolyzed with aqueous sulfuric acid.An improved procedure for this final hydrolysis step uses 1,1,2-trichloroethane as co-solvent.
参考文献标题:Process for producing ioversol
文献作者:Dunn,T.J.; White,D.H.; Kneller,M.T.; Jones,M.M.; Doran,N.O.III; Bailey,A.R.(Mallinckrodt Medical Inc.)
参考来源:WO 9727172
合成路线:Chlorination of 5-amino-2,4,6-triiodoisophthalic acid (I) with SOCl2 in EtOAc or toluene affords acid chloride (II).Yields have been improved with the addition of benzyltriethylammonium chloride as a catalyst.Acid chloride (II) is then condensed with 3-amino-1,2-propanediol (III) to produce diamide (IV).Compound (IV) is converted to the tetraacetate ester (V) employing acetic anhydride in pyridine.Subsequent acylation of the amino group of (V) with acetoxyacetyl chloride (VI) gives amide (VII).After saponification of the ester groups of (VII),the resultant hydroxy acetamide (VIII) is alkylated by 2-chloroethanol (IX) to furnish the title compound.Alternatively,amide (VIII) is alkylated by bromoethyl acetate (X),producing (XI).Hexa-ester (XI) is finally hydrolyzed with aqueous sulfuric acid.An improved procedure for this final hydrolysis step uses 1,1,2-trichloroethane as co-solvent.
参考文献标题:Process for the preparation of 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorination with thionyl chloride in the presence of a catalyst
文献作者:Villa,M.; Castaldi,G.; Pozzoli,C.; Russo,L.(Zambon Group SpA)
参考来源:WO 9636590
合成路线:Chlorination of 5-amino-2,4,6-triiodoisophthalic acid (I) with SOCl2 in EtOAc or toluene affords acid chloride (II).Yields have been improved with the addition of benzyltriethylammonium chloride as a catalyst.Acid chloride (II) is then condensed with 3-amino-1,2-propanediol (III) to produce diamide (IV).Compound (IV) is converted to the tetraacetate ester (V) employing acetic anhydride in pyridine.Subsequent acylation of the amino group of (V) with acetoxyacetyl chloride (VI) gives amide (VII).After saponification of the ester groups of (VII),the resultant hydroxy acetamide (VIII) is alkylated by 2-chloroethanol (IX) to furnish the title compound.Alternatively,amide (VIII) is alkylated by bromoethyl acetate (X),producing (XI).Hexa-ester (XI) is finally hydrolyzed with aqueous sulfuric acid.An improved procedure for this final hydrolysis step uses 1,1,2-trichloroethane as co-solvent.
参考文献标题:Process for production of ioversol
文献作者:Lin,Y.; Dean,R.T.; Kneller,M.; Wallace,R.A.; McCarthy,W.Z.; White,D.H.(Mallinckrodt Medical Inc.)
参考来源:WO 9111431
合成路线:Chlorination of 5-amino-2,4,6-triiodoisophthalic acid (I) with SOCl2 in EtOAc or toluene affords acid chloride (II).Yields have been improved with the addition of benzyltriethylammonium chloride as a catalyst.Acid chloride (II) is then condensed with 3-amino-1,2-propanediol (III) to produce diamide (IV).Compound (IV) is converted to the tetraacetate ester (V) employing acetic anhydride in pyridine.Subsequent acylation of the amino group of (V) with acetoxyacetyl chloride (VI) gives amide (VII).After saponification of the ester groups of (VII),the resultant hydroxy acetamide (VIII) is alkylated by 2-chloroethanol (IX) to furnish the title compound.Alternatively,amide (VIII) is alkylated by bromoethyl acetate (X),producing (XI).Hexa-ester (XI) is finally hydrolyzed with aqueous sulfuric acid.An improved procedure for this final hydrolysis step uses 1,1,2-trichloroethane as co-solvent.
参考文献标题:Improved synthesis of ioversol
文献作者:Kneller,M.T.; Bailey,A.R.; Sathe,S.S.; Spears,A.T.; Wisneski,R.C.(Mallinckrodt Medical Inc.)
参考来源:WO 9323365
合成路线:In a related method,the intermediate tetrahydroxy amine (I) is acylated by chloroacetyl chloride (II) to produce the penta(chloroacetyl) derivative (III).The chloroacetate ester groups are then hydrolyzed under basic conditions to afford the tetra-hydroxy chloroacetamide (IV).Conversion of (IV) to the hydroxy acetamide (V) is accomplished by treatment with sodium acetate and NaOH.Amide (V) is finally alkylated with either chloroetanol (VI) or with ethylene oxide (VII) to furnish the title N-(hydroxyethyl) amide.
参考文献标题:Process for producing ioversol
文献作者:Dunn,T.J.; Kneller,M.T.; White,D.H.; Jones,M.M.; Doran,N.O.(Mallinckrodt Medical Inc.)
参考来源:WO 9640286
产品链接: CAS No. 87771-40-2››