Hydrogen Bromide → Biotin

Participants

Reaction Steps

A mixture of 3.0 g of (3aS,4S,6aR)-1,3-dibenzyl-hexahydro-2-oxo-4H-thieno[3,4-d]imidazol-4-pentanoic acid and 24 ml of 48% hydrobromic acid was refluxed at 110° C. to 120° C. for 48 hours. Hot extraction with 10 ml of toluene was carried out four times to remove benzyl bromide. The aqueous layer was concentrated, 15 ml of water and 11.5 ml of 6M aqueous sodium hydroxide solution were added to the residue, subsequently 3.36 g of ethoxycarbonyl chloride was added dropwise, and the reaction was carried out while maintaining pH to 8 to 10, at room temperature for 3 hours. Thereafter, a temperature of the reaction mixture was raised to 70° C. to 80° C., and the reaction was carried out for 20 hours (during the reaction, pH was maintained to 12 by adding 6M aqueous sodium hydroxide solution). pH was adjusted to 7.4 to 7.8 with 7 ml of 16% hydrochloric acid, and filtration was carried out at 90° C. to 95° C. by using 1.0 g of activated charcoal. The filtrate was heated to 80° C. to 85° C., pH thereof was adjusted to 1.8 to 2.2 by using 6 ml of 16% hydrochloric acid, and neutralization crystallization was carried out. After cooling, crystal was collected by filtration and washed with water, and dried by blowing air at 50° C. to give 1.38 g of (+)-biotin as colorless crystal.

Provenance & Evidence