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

반응식

CC(N[CH2:6][C@H:7]([OH:21])[CH2:8][O:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:19](=[O:20])[CH2:18][CH2:17][CH2:16][C:15]=12)(C)C.CC(NC[C@@H](O)COC1C=CC=[C:35]2[C:40](=[O:41])CCCC=12)(C)C.C(N)(C)(C)C.OC1C=CC=C2C=1CCCC2=O.C([C@@H]1OC1)Cl>>[O:21]1[CH2:6][C@H:7]1[CH2:8][O:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:15]=1[CH2:16][CH2:17][CH2:18][C:19]2=[O:20].[O:41]1[CH2:40][CH2:35]1

참가 물질

반응물 5

HCID 6385Tert-Butylamine

HCID 39468Levobunolol

HCID 1199215-Hydroxy-1-tetralone

HCID 2734062(-)-Epichlorohydrin

HCID 5460339Bunolol, (R)-

생성물 1

HCID 86748747oxirane (S)-5-(2,3-epoxypropoxy)-3,4-dihydro-1(2H)-naphthalenone

실험 절차

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.