Cl.[Cl:2][C:3]1[CH:17]=[CH:16][CH:15]=[CH:14][C:4]=1[CH2:5][NH:6][CH2:7][CH2:8][C:9]1[S:10][CH:11]=[CH:12][CH:13]=1.Cl.[CH3:19]OCOC.[OH-].[Na+]>CN(C)C=O.O.C1(C)C=CC=CC=1>[ClH:2].[Cl:2][C:3]1[CH:17]=[CH:16][CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:7][CH2:8][C:9]2[S:10][CH:11]=[CH:12][C:13]=2[CH2:19]1
N-(2-chlorobenzyl)-2-(2-thienyl)-ethylamine hydrochloride (29.2 g, 102 mmole), hydrogen chloride gas (4.5 g, 129 mmoles) and dimethoxymethane (33 ml, 388 mmoles) were combined in dimethylformamide (57 ml). The solution was refluxed and stirred for 11 hours. The dimethylformamide was removed under vacuum while keeping the temperature of the solution at 85° C. A solution of sodium hydroxide (11 g, 275 mmoles) in H2O (87 ml) and toluene (87 ml) was added to the residue and stirred at a temperature less than 55° C. for 30 minutes. The aqueous and organic layers were separated and the aqueous layer washed with toluene (85 ml). The toluene was combined with the organic layer and concentrated under vacuum to 50 ml. The solution was filtered to remove salts. Methanol (17 ml) and HCl gas were added to the solution at a temperature less than 40° C. until a pH of 1.5 was reached. The slurry was heated to a temperature less than 50° C. for one hour and cooled to 0° C. for one hour. The product was isolated, washed with 1:9 methanol/toluene and dried; yielding 87.6% real to real (corrected for assay of starting material) of 5-(2-chlorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride (ticlopidine hydrochloride). Characterizing HPLC data indicated 99.3% pure.
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