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.

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.

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.

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.

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.

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.

Asymmetric addition of trimethylsilyl cyanide to 4,5-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.

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. 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.