The condensation of ethyl 4-methylbenzoate (I) with 2-(2-bromoethyl)-1,3-dioxolane (II) by means of lithium diisopropylamide gives ethyl 4-[3-(1,3-dioxolan-2-yl)propyl]benzoate (III), which is hydrolyzed to ethyl 4-(3-formylpropyl)benzoate (IV). The condensation of (IV) with 1-(2-aminoethyl) cyclohexanol (V) affords the corresponding imine (VI), which is cyclized with methyl thioglycolate (VII) yielding ethyl 4-[3-[3-[2-[1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]propyl]benzoate (VIII) . The hydrolysis of (VIII) with KOH gives L-644122 as a racemic mixture (IX), which is methylated with MeI and K2CO3 to the corresponding methyl ester (X). Esterification of (X) with (-)-camphanic acid (XI) by means of dicyclohexylcarbodumide in methylene chloride affords the diastereomeric mixture of esters (XII), which is separated into its components by fractionated crystallization in ethyl acetate hexane. Finally, the (+)-diastereomer (XIII) is hydrolyzed with KOH in refluxing toluene containing diclohexyl-18-crown-6.

The condensation of ethyl 4-methylbenzoate (I) with 2-(2-bromoethyl)-1,3-dioxolane (II) by means of lithium diisopropylamide gives ethyl 4-[3-(1,3-dioxolan-2-yl)propyl]benzoate (III), which is hydrolyzed to ethyl 4-(3-formylpropyl)benzoate (IV). The condensation of (IV) with 1-(2-aminoethyl) cyclohexanol (V) affords the corresponding imine (VI), which is cyclized with methyl thioglycolate (VII) yielding ethyl 4-[3-[3-[2-[1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]propyl]benzoate (VIII) . The hydrolysis of (VIII) with KOH gives L-644122 as a racemic mixture (IX), which is methylated with MeI and K2CO3 to the corresponding methyl ester (X). Esterification of (X) with (-)-camphanic acid (XI) by means of dicyclohexylcarbodumide in methylene chloride affords the diastereomeric mixture of esters (XII), which is separated into its components by fractionated crystallization in ethyl acetate hexane. Finally, the (+)-diastereomer (XIII) is hydrolyzed with KOH in refluxing toluene containing diclohexyl-18-crown-6.

The condensation of ethyl 4-methylbenzoate (I) with 2-(2-bromoethyl)-1,3-dioxolane (II) by means of lithium diisopropylamide gives ethyl 4-[3-(1,3-dioxolan-2-yl)propyl]benzoate (III), which is hydrolyzed to ethyl 4-(3-formylpropyl)benzoate (IV). The condensation of (IV) with 1-(2-aminoethyl) cyclohexanol (V) affords the corresponding imine (VI), which is cyclized with methyl thioglycolate (VII) yielding ethyl 4-[3-[3-[2-[1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]propyl]benzoate (VIII) . The hydrolysis of (VIII) with KOH gives L-644122 as a racemic mixture (IX), which is methylated with MeI and K2CO3 to the corresponding methyl ester (X). Esterification of (X) with (-)-camphanic acid (XI) by means of dicyclohexylcarbodumide in methylene chloride affords the diastereomeric mixture of esters (XII), which is separated into its components by fractionated crystallization in ethyl acetate hexane. Finally, the (+)-diastereomer (XIII) is hydrolyzed with KOH in refluxing toluene containing diclohexyl-18-crown-6.

The condensation of ethyl 4-methylbenzoate (I) with 2-(2-bromoethyl)-1,3-dioxolane (II) by means of lithium diisopropylamide gives ethyl 4-[3-(1,3-dioxolan-2-yl)propyl]benzoate (III), which is hydrolyzed to ethyl 4-(3-formylpropyl)benzoate (IV). The condensation of (IV) with 1-(2-aminoethyl) cyclohexanol (V) affords the corresponding imine (VI), which is cyclized with methyl thioglycolate (VII) yielding ethyl 4-[3-[3-[2-[1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]propyl]benzoate (VIII) . The hydrolysis of (VIII) with KOH gives L-644122 as a racemic mixture (IX), which is methylated with MeI and K2CO3 to the corresponding methyl ester (X). Esterification of (X) with (-)-camphanic acid (XI) by means of dicyclohexylcarbodumide in methylene chloride affords the diastereomeric mixture of esters (XII), which is separated into its components by fractionated crystallization in ethyl acetate hexane. Finally, the (+)-diastereomer (XIII) is hydrolyzed with KOH in refluxing toluene containing diclohexyl-18-crown-6.