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N-(2-chlorobenzyl )-2-(2-thienyl)-ethylamine hydrochloride (29.2g, 102mmole), hydrogen chloride gas (4.5g, 129mmoles) and dimethoxymethane (33ml, 388mmoles) were combined in dimethylformamide (57ml). 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 (11g, 275mmoles) in H2O (87ml) and toluene (87ml) 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 (85ml). The toluene was combined with the organic layer and concentrated under vacuum to 50ml. The solution was filtered to remove salts. Methanol (17ml) 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.

1. temperatureThe solution was refluxed
2. customThe dimethylformamide was removed under vacuum
3. customat 85° C
4. stirringstirred at a temperature less than 55° C. for 30 minutes
5. customThe aqueous and organic layers were separated
6. washthe aqueous layer washed with toluene (85ml)
7. concentrationconcentrated under vacuum to 50ml
8. filtrationThe solution was filtered
9. customto remove salts
10. additionMethanol (17ml) and HCl gas were added to the solution at a temperature less than 40° C. until a pH of 1.5
11. temperatureThe slurry was heated to a temperature less than 50° C. for one hour
12. customThe product was isolated
13. washwashed with 1:9 methanol/toluene
14. customdried