189683-97-4Relevant articles and documents
Synthesis of the Adrenergic Bronchodilators (R)-Terbutalinel and (R)-Salbutamol from (R)-Cyanohydrins
Effenberger, Franz,Jaeger, Juergen
, p. 3867 - 3873 (2007/10/03)
Stereoselective syntheses of (R)-terbutaline and (R)-salbutamol acetal, which are important bronchodilators, starting from O-protected (R)-cyanohydrins are described. (R)-Terbutaline hydrochloride (R)-9·HCl is obtained in an overall yield of 44% with >98% ee from the O-bisallyl-protected cyanohydrin (R)-4k via a Ritter N-tertiary butylation to the amide (R)-6a, hydrogenation to the amino alcohol (R)-7a, and deprotection of the hydroxyl functions. (R)-Salbutamol acetals (R)-7b,c can be obtained from the corresponding O-protected (R)-cyanohydrins either via the route described for (R)-terbutaline or via selective hydrogenation of the protected cyanohydrin (R)-11 to the imino derivative, transimination with tert-butylamine, followed by hydrogenation with NaBH4 to give the 2-amino alcohol derivative (R)-12. Desilylation of (A)-12 to (R)-7c is performed with LiAlH4. Hydrolytic cleavage of the acetals (A)-7b and c to (R)-salbutamol was not yet possible without racemization.
