Thiophenes, hydroxy-, chlorination

Cyclocondensation of 3-(alkylthio)isonicotinic acid derivatives catalyzed by strong bases also provides a convenient method for thiophene ring closure. For example, treatment of isonicotinate 215 with sodium hydride produced thienopyridine 216 (1991USP4904672). Cyclization of isonicotinamide 217 in the presence of an excess of MeONa is accompanied by the nucleophilic substitution of the chlorine atom to give finally 3-hydroxy-7-methoxy-2-phenylthieno[2,3-c]pyridine (218) (1993TL2875). 

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