Novel process for the manufacture of thiophene derivatives suited for the manufacture of biotin, process for the manufacture of biotin and novel intermediates in this process

Claim 1

Process for the manufacture of novel thiophene derivatives and of biotin, respectively, characterized in that a compound of the general formula wherein R 2 is aryl-lower alkyl, is heated at a temperature of from about 50°C to about 200°C in an inert organic solvent, or in that the compound of the formula is heated with an aryl-lower alkyl hydroxylamine at a temperature of from about 80° to about 150°C, that, if desired, a so obtained compound of the general formula wherein R 2 has the above meaning, is catalytically hydrogenated or treated with zinc powder in a lower alkanoic acid, that, if desired, a so obtained compound of the general formula wherein R 2 has the above meaning, is acylated, that, if desired, a so obtained compound of the general formula wherein R 2 has the above meaning and R 4 is lower alkyl, aryl or aryl-lower alkyl, is treated with a base, that, if desired, a so obtained compound of the general formula wherein R 2 has the above meaning, is esterified, that, if desired, a so obtained compound of the general formula wherein R 2 has the above meaning and R 6 is lower alkyl or aryl-lower alkyl, is halogenated, that, if desired, a so obtained compound of the general formula wherein R 2 and R 6 have the above meanings and X is halogen, is treated with a non- nucleophilic organic base, that, if desired, a so obtained compound of the general formula wherein R 2 and R 6 have the above meanings, is catalytically hydrogenated, with or without previous saponification, that, if desired, a so obtained compound of the general formula wherein R 2 has the above meaning and R '6 is hydrogen, lower alkyl or aryl-lower alkyl, is converted into biotin according to methods known per se.