新产品编号:1859359

Chemical Name: 4-Fluoro-5-[1(R)-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol oxalate
项目整合开发状态: Biological Testing
项目研究机构: National Institutes of Health (Originator), Westf鋖ische Wilhelms-Univ. M黱ster (Originator)
合成路线:The condensation of 3,4-dibenzyloxy-2-fluorobenzaldehyde (I) with dichloromethyl phenylsulfoxide (II) in the presence of LDA at -78 C afforded adduct (III) which,upon treatment with ethylmagnesium bromide gave rise to chloroketone (IV).Asymmetric carbonyl reduction of (IV) employing borane and the chiral oxazaborolidine catalyst (V) provided the (R)-chloroalcohol (VI).After conversion of (VI) to azide (VII),catalytic hydrogenation in the presence of Pd/C and oxalic acid yielded the title compound.

合成路线:Asymmetric addition of trimethylsilyl cyanide to 3,4-dibenzyloxy-2-fluorobenzaldehyde (I) employing the chiral (R,R)-salen ligand (II) in the presence of titanium tetraisopropoxide generated the chiral O-trimethylsilyl cyanohydrin (III),which was subsequently reduced to the desired (S)-aminoalcohol (IV) by means of LiAlH4.The benzyl protecting groups of (IV) were then removed by hydrogenolysis to furnish the title compound.

合成路线:The condensation of 4,5-dibenzyloxy-2-fluorobenzaldehyde (I) with dichloromethyl phenylsulfoxide (II) in the presence of LDA at -78 C afforded adduct (III) which,upon treatment with ethylmagnesium bromide gave rise to chloroketone (IV).Asymmetric carbonyl reduction of (IV) employing borane and the chiral oxazaborolidine catalyst (V) provided the (R)-chloroalcohol (VI).After conversion of (VI) to azide (VII),catalytic hydrogenation in the presence of Pd/C and oxalic acid yielded the title compound.

合成路线:Asymmetric addition of trimethylsilyl cyanide to 4,5-dibenzyloxy-2-fluorobenzaldehyde (I) employing the chiral (R,R)-salen ligand (II) in the presence of titanium tetraisopropoxide generated the chiral O-trimethylsilyl cyanohydrin (III),which was subsequently reduced to the desired (S)-aminoalcohol (IV) by means of LiAlH4.The benzyl protecting groups of (IV) were then removed by hydrogenolysis to furnish the title compound.

合成路线:Asymmetric addition of trimethylsilyl cyanide to 3,4-dibenzyloxy-2-fluorobenzaldehyde (I) employing the chiral (S,S)-salen ligand (II) in the presence of titanium tetraisopropoxide generated the chiral O-trimethylsilyl cyanohydrin (III),which was subsequently reduced to the desired (R)-aminoalcohol (IV) by means of LiAlH4.Heating of (IV) with ethyl formate provided formamide (V),which was reduced to the N-methyl amine (VI) with LiAlH4 in refluxing THF.The benzyl protecting groups of (VI) were finally removed by hydrogenolysis to furnish the title compound.

合成路线:Asymmetric addition of trimethylsilyl cyanide to 3,4-dibenzyloxy-2-fluorobenzaldehyde (I) employing the chiral (R,R)-salen ligand (II) in the presence of titanium tetraisopropoxide generated the chiral O-trimethylsilyl cyanohydrin (III),which was subsequently reduced to the desired (S)-aminoalcohol (IV) by means of LiAlH4.Heating of (IV) with ethyl formate provided formamide (V),which was reduced to the N-methyl amine (VI) with LiAlH4 in refluxing THF.The benzyl protecting groups of (VI) were finally removed by hydrogenolysis to furnish the title compound.