Abstract: The invention relates to a new, industrially advantageous, process for the preparation of the known beta-adrenergic blocking agent, levobunolol, not requiring resolution of racemic bunolol, based on the enantioselective synthesis of an oxiranic intermediate which is then reacted with tert-butylamine. It consists of reacting 5-hydroxy-3,4-dihydro-1(2H)-naphthalenone with (R)-(-)epichlorhydrine in an aprotic solvent, in the presence of a strong base at a temperature of over 90.degree. C., thus obtaining the intermediate chiral oxirane (S)-5-(2,3-epoxypropoxy)-3,4-dihydro-1-(2H)-naphthalenone with more than 95% optical purity, and then, the intermediate chiral oxirane is reacted with tert-butylamine.
Type:
Grant
Filed:
March 16, 1994
Date of Patent:
June 20, 1995
Assignee:
Medicham, S.A.
Inventors:
Alberto Stampa Diez Del Corral, Pelayo Camps Garcia, Maria del Carmen Onrubia Miguel, Carmen Arnalot Aguilar