Process for preparing biotin

Claim 1

The process of preparing biotin which comprises a. ozonizing a lower alkoxycyclohexene to form the lower alkyl ester of 6-oxohexanoic acid; b. reacting nitromethane with the lower alkyl ester of 6-oxo-hexanoic acid from step (a) under basic conditions in the presence of a solvent suitable for nitromethylation to form the lower alkyl ester of 7-nitro-6-hydroxy-heptanoic acid; c. reacting the product of step (b) with a lower alkanoic acid or its halide or anhydride derivative to form the lower alkyl ester of 7-nitro-6-lower alkanoyl -heptanoic acid; d. placing the reaction product of step (c) in a suitable solvent under basic conditions at slightly raised temperatures to form the lower alkyl ester of 7-nitrohept-6-enoic acid; e. reacting nitroethanethiol with the reaction product from step (d) in an inert atmosphere, in a solvent and under conditions suitable for nucleophilic addition to form the lower alkyl ester of dl-7-thio-6-nitromethyl-9-nitrononanoic acid; f. reactively contacting the reaction product of step (e) with a catalytic amount of a tertiary alkyl amine and phosphorus oxychloride under substantial anhydrous conditions in a substantially inert atmosphere in a suitable solvent to form dl-6-(4-carbo lower alkoxy-butyl)-4H-6H-thieno [3,4-d]-furoxan; g. reducing the product from step (f) by catalytic hydrogenation or by using a suitable reducing agent and acylating with a suitable carboxylic acid of one to four carbon atoms or its acid chloride or anhydride derivative, said acid or its derivative being substituted with from 0 to 3 halogens, to form dl-2(4-carbo lower alkoxy-butyl)-3,4-bis(alkamido)-2,5-dihydro-thiophene; h. selectively hydrogenating the product from step (g) to form dl-cis-2(4-carbo lower alkoxy-butyl)-3,4-cis-bis(alkamido)-tertrahydro-thiophene; i. hydrolyzing and cyclizing the product from step (h) to form dl-biotin.