Back to results
US 5,847,152 AGranted
Preparation of a D-(+)-biotin intermediate
AssigneeMerck Patent GmbH
InventorsJurgen Eckstein, Thomas Koppe, Michael Schwarz, Michael Casutt
Life of this patent
Estimating the term…
Abstract
The present invention relates to an improved process for making heterocyclic compounds suitable for intermediate products for making D-(+)-biotin and a process for making D-(+)-biotin itself.
Claims14
An improved process for the preparation of a D-(+)-biotin intermediate of the formula I ##STR4## in which R is H or C.sub.1-6 -alkyl,
- by reacting a thiolactone of the formula II ##STR5## in which R has the meaning indicated, with 1,4-dimagnesiumchlorobutane and carbon dioxide in an inert solvent and subsequently eliminating water using a mineral acid, wherein the following steps are carried out successively:
- a) reacting 1,4-dichlorobutane with magnesium turnings in the presence of catalytic amounts of 1,2-dibromoethane in tetrahydrofuran as a solvent,
- b) adding thereto the thiolactone of the formula II, dissolved in tetrahydrofuran at temperatures between -25.degree. and -15.degree. C., and, if appropriate, subsequently stirring,
- c) passing over CO.sub.2 at temperatures between -25.degree. and -15.degree. C.,
- d) adding sulfuric acid for neutralization and dehydration,
- e) separating the phases and concentrating under reduced pressure,
- f) dissolving the residue in a hydrocarbon solvent and washing the organic phases with aqueous alkali,
- g) acidifying the aqueous phase with a mineral acid and extracting the aqueous phase with a hydrocarbon, and
- h) concentrating the organic phase remaining from g) under reduced pressure.
6 more elements
Dependencies are inferred from the claim text.