The title product can be obtained in several steps: 1) (+)-2-(2-Chlorophenyl)glycine methyl ester [(+)-IV] is prepared as follows: a) Racemic 2-(2-chlorophenyl)glycine (I) is methylated with methanol - HCl to the methyl ester (II), which is resolved with (+)-tartaric acid to the active ester [(+)-IV]. b) Racemic (I) is resolved with (+)-10-camphorsulfonic acid to (+)-2-(2-chlorophenyl)glycine [(+)-III], which is then esterified as before to [(+)-IV]. 2) (+)-2-(2-Chlorophenyl)-N-[2-(2-thienyl)ethyl]glycine methyl ester [(+)-VII] is prepared as follows: a) Alkylation of [(+)-IV] with 2-[2-(phenylsulfonyloxy)ethyl]thiophene (V) or with 2-(2-bromoethyl)thiophene (VI). b) Optical resolution of racemic alkylated glycine ester (VIII) with (+)-10-camphorsulfonic acid. 3) Finally, (+)-clopidogrel is prepared as follows: a) Cyclization of active [(+)-VII] with formaldehyde - formic acid and aqueous HCl. b) Cyclization of racemic (VIII) as before, yielding racemic clopidogrel (PCR-4099), followed by optical resolution with (+)-10-camphorsulfonic acid.

The title product can be obtained in several steps: 1) (+)-2-(2-Chlorophenyl)glycine methyl ester [(+)-IV] is prepared as follows: a) Racemic 2-(2-chlorophenyl)glycine (I) is methylated with methanol - HCl to the methyl ester (II), which is resolved with (+)-tartaric acid to the active ester [(+)-IV]. b) Racemic (I) is resolved with (+)-10-camphorsulfonic acid to (+)-2-(2-chlorophenyl)glycine [(+)-III], which is then esterified as before to [(+)-IV]. 2) (+)-2-(2-Chlorophenyl)-N-[2-(2-thienyl)ethyl]glycine methyl ester [(+)-VII] is prepared as follows: a) Alkylation of [(+)-IV] with 2-[2-(phenylsulfonyloxy)ethyl]thiophene (V) or with 2-(2-bromoethyl)thiophene (VI). b) Optical resolution of racemic alkylated glycine ester (VIII) with (+)-10-camphorsulfonic acid. 3) Finally, (+)-clopidogrel is prepared as follows: a) Cyclization of active [(+)-VII] with formaldehyde - formic acid and aqueous HCl. b) Cyclization of racemic (VIII) as before, yielding racemic clopidogrel (PCR-4099), followed by optical resolution with (+)-10-camphorsulfonic acid.

The condensation of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (I) with 2-chlorobenzaldehyde (II) by means of either KCN/HCl, KCN/AcOH, NaHSO3/KCN, NaHSO3 /NaCN, NaHSO3/Tms-CN, NaCN/HCl or AcOH/cyclo[(S)-His-(S)-Phe] and HCN purge gives 2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)acetonitrile (III), which is hydrolyzed to the corresponding acetamide (IV) by means of either KOH, NaOH, NaOH followed by H2O2, refluxing HCl/TFA, formic acid/HCl, refluxing HBr, refluxing H2SO4 or refluxing HClO4. Finally, compound (III) is converted into the corresponding methyl ester with MeOH and either dimethylformamide dimethylacetal, H2SO4, Ms-OH, PPA, TiCl4, POCl3 or HCl.

The title product can be obtained in several steps: 1) (+)-2-(2-Chlorophenyl)glycine methyl ester [(+)-IV] is prepared as follows: a) Racemic 2-(2-chlorophenyl)glycine (I) is methylated with methanol - HCl to the methyl ester (II), which is resolved with (+)-tartaric acid to the active ester [(+)-IV]. b) Racemic (I) is resolved with (+)-10-camphorsulfonic acid to (+)-2-(2-chlorophenyl)glycine [(+)-III], which is then esterified as before to [(+)-IV]. 2) (+)-2-(2-Chlorophenyl)-N-[2-(2-thienyl)ethyl]glycine methyl ester [(+)-VII] is prepared as follows: a) Alkylation of [(+)-IV] with 2-[2-(phenylsulfonyloxy)ethyl]thiophene (V) or with 2-(2-bromoethyl)thiophene (VI). b) Optical resolution of racemic alkylated glycine ester (VIII) with (+)-10-camphorsulfonic acid. 3) Finally, (+)-clopidogrel is prepared as follows: a) Cyclization of active [(+)-VII] with formaldehyde - formic acid and aqueous HCl. b) Cyclization of racemic (VIII) as before, yielding racemic clopidogrel (PCR-4099), followed by optical resolution with (+)-10-camphorsulfonic acid.

The reaction of [benzene-U-13C]benzoic acid (I) with SOCl2 gives the corresponding acyl chloride (II), which is cyclized with the ethanolamine (III) to yield the oxazoline (IV).The chlorination of (IV) with sec-BuLi and hexachloroethane in toluene affords the 2-chlorophenyl derivative (V), which is methylated with MeI to provide the oxazolinium salt (VI). The reduction of (VI) with NaBH4 in ethanol yields the oxazolidine (VII), which is hydrolyzed with HCl to afford the labeled 2-chlorobenzaldehyde (VIII). The condensation of aldehyde (VIII) with the tetrahydrothienopyridine (IX) by means of acetone cyanohydrine in hot toluene affords the substituted acetonitrile (X), which is hydrolyzed to the substituted acetamide (XI) with HCl in methanol. Finally, this compound is treated with H2SO4 in refluxing methanol to afford the target labeled methyl ester as a racemic mixture.

The reaction of [benzene-U-13C]benzoic acid (I) with SOCl2 gives the corresponding acyl chloride (II), which is cyclized with the ethanolamine (III) to yield the oxazoline (IV).The chlorination of (IV) with sec-BuLi and hexachloroethane in toluene affords the 2-chlorophenyl derivative (V), which is methylated with MeI to provide the oxazolinium salt (VI). The reduction of (VI) with NaBH4 in ethanol yields the oxazolidine (VII), which is hydrolyzed with HCl to afford the labeled 2-chlorobenzaldehyde (VIII). The condensation of aldehyde (VIII) with the tetrahydrothienopyridine (IX) by means of acetone cyanohydrine in hot toluene affords the substituted acetonitrile (X), which is hydrolyzed to the substituted acetamide (XI) with HCl in methanol. Finally, this compound is treated with H2SO4 in refluxing methanol to afford the target labeled methyl ester as a racemic mixture.

The title product can be obtained in several steps: 1) (+)-2-(2-Chlorophenyl)glycine methyl ester [(+)-IV] is prepared as follows: a) Racemic 2-(2-chlorophenyl)glycine (I) is methylated with methanol - HCl to the methyl ester (II), which is resolved with (+)-tartaric acid to the active ester [(+)-IV]. b) Racemic (I) is resolved with (+)-10-camphorsulfonic acid to (+)-2-(2-chlorophenyl)glycine [(+)-III], which is then esterified as before to [(+)-IV]. 2) (+)-2-(2-Chlorophenyl)-N-[2-(2-thienyl)ethyl]glycine methyl ester [(+)-VII] is prepared as follows: a) Alkylation of [(+)-IV] with 2-[2-(phenylsulfonyloxy)ethyl]thiophene (V) or with 2-(2-bromoethyl)thiophene (VI). b) Optical resolution of racemic alkylated glycine ester (VIII) with (+)-10-camphorsulfonic acid. 3) Finally, (+)-clopidogrel is prepared as follows: a) Cyclization of active [(+)-VII] with formaldehyde - formic acid and aqueous HCl. b) Cyclization of racemic (VIII) as before, yielding racemic clopidogrel (PCR-4099), followed by optical resolution with (+)-10-camphorsulfonic acid.