Reacción #50363

Ecuación de reacción

levobunolol

bunolol

5-hydroxy-3,4-dihydro-1(2H)-naphthalenone

(R)-(-)epichlorhydrine

tert-butylamine

→

oxirane (S)-5-(2,3-epoxypropoxy)-3,4-dihydro-1-(2H)-naphthalenone

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrofor the preparation of the known
2. 2
   Otrobased on the enantioselective synthesis of an oxiranic intermediate which

Procedimiento

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° 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.

Fuente