Investigation On Synthesis Of Bupropion, Hydroxybupropion And Their Analogs

Bupropion and hydroxybupropion were novel antidepressant. Novel antidepressant, bupropion, hydroxybupropion and their analogs were synthesized via a -bromination ,aminization of 2-amino-2-methyl-propanol and N-methylethanolamine from 3-chloropropiophenone, propiophenone, (4-benzyloxy)-l-propiophenone and (6-methoxy-2-naphthyl)-1- propiophenone.Intermediate,2-bromo-(3-chlorophenyl)-1-propiophenone,2-chloro-(3-chlorophen yl) -1-propiophenone that was synthesized via a -halogenation with CuX2 reacted with tert-butylamine in NMP at ambience to give antidepressant ,bupropion .The reacting time was cut short to 1 h from hours,days in NMP solvent. (+)-Isomer of bupropion was first asymmetrically synthesized with chiral auxiliary (2S,3S)-(-)-dimethyl tartrate from readily available 3-chloropropiophenone in china.The route was simple , available and met the tendency of administer using optically pure isomer. So,it had significance of reality .2-Bromo-phenyl-1 -propiophenone,2-(4-benzyloxy)-1 -propiophenone and 2-(6-methoxy-2-naphthyl)-1-propiophenone respectively reacted with tert-butylamine in NMP to give l-phenyl-2-[(1,1-dimethylethyl)amino]-1-propanone,1-(4-benzyloxy)-2-[(1,1-dimethylethyl)amino]-1-propanoneand 1-(6-methoxy-2-naphthyl)-2-[(1,1-dimethylethyl) amino]-1-propanone in high yield.The novel antidepressant , hydroxybupropion was synthesized first in NMP via 2-bromo-(3-chlorophenyl)-1-propiophenone from 3-chloropropiophenone in china. The route had the advantage of short time,high-yield and easy-operation.The novel analogs of hydroxybupropion ,2-phenyl-3,5,5-trimethyl-2-morpholinol, 2-(4-benzyloxy)-3,5,5-trimethyl-2-morpholinol,and2-(6-methoxy-2-naphthyl)-3,5,5-trimethyl-2-morpholinol were first synthesized in china by 2-bromo-phenyl-1-propiophenone,2-bromo-(4-benzyloxy)-1-propiophenone and 2-bromo-(6-methoxy-2-naphthyl)-1- propiophenone reacting with 2-amino-2-methyl-propanol in high yield .2-Bromo-(3-chlorophenyl)-1-propiophenone,2-bromo-phenyl-1-propiophenone, 2-bromo-(4-benzyloxy)-l -propiophenone and 2-bromo-(6-methoxy-2-naphthyl)-1 -propiophenone reacted in NMP with N-methylethanolamine to give four novelcompounds in high yield:2-(3-chlorophenyl)-3,4-dimethyl-2-morpholinol,2-phenyl-3,4 dimethyl-2-morpholinol,2-(4-benzyloxy)-3,4-dimethyl-2-morpholinol,2-(6-methoxy-2-naphthyl)-3,4-dimethyl-2-morpholinol.