A concise enantioselective synthesis of 1-[(S)-3-(dimethylamino)-3,4-dihydro-6,7-dimethoxyquinolin-1(2H)-yl]propan-1-one, (S)-903

A concise enantioselective synthesis of (S)-903, an inotropic agent, is described in nine linear steps and 95% ee based on asymmetric dihydroxylation of cinnamate ester and Co-catalyzed multifunctional reduction of several functional groups leading to the construction of core tetrahydroquinolin-3-ol, as the key steps.

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(2R,3S)-Ethyl 2,3-dihydroxy-3-(3,4-dimethoxyphenyl)propanoateC13H18O6[α]D25=+3.5 (c 1.5, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S)

(2R,3S)-Ethyl 2,3-dihydroxy-3-(4,5-dimethoxy-2-nitrophenyl)propanoateC13H17NO8[α]D25=+105.2 (c 1, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S)

(R)-1,2,3,4-Tetrahydro-6,7-methoxyxyquinolin-3-olC9H11NO[α]D25=+11.2 (c 1, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (3R)

1-[(R)-3,4-Dihydro-3-hydroxy-6,7-dimethoxyquinolin-1(2H)-yl]propan-1-oneC14H19NO4Ee 95% determined by chiral HPLC[α]D25=+8.7 (c 1.15, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (3R)

1-[(R)-3-Azido-3,4-dihydro-6,7-dimethoxyquinolin-1(2H)-yl]propan-1-oneC14H18N4O3[α]D25=+38.2 (c 2, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (3S)

1-[(S)-3-(Dimethylamino)-3,4-dihydro-6,7-dimethoxy-quinolin-1(2H)-yl]propan-1-oneC16H24N2O3[α]D25=-3.2 (c 1, EtOH)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (3S)