CHIRAL SYNTHESIS OF N--1-[2,3-DIHYDROXY-PROPYL]CYCLOPROPANESULFONAMIDES

摘要

The present invention relates to a novel enantioselective method of preparing (S)- and (R)-enantiomers of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-5 methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamide, to novel intermediate compounds, and to the use of said novel intermediate compounds for the preparation of said (S)- and (R)-enantiomers of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamide.;

主权项

1. A compound selected from:
1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropanesulfonyl bromide (S)-10-Br: 1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropanesulfonyl bromide (R)-10-Br: potassium 1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropane-sulfonate (S)-7′: potassium 1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropane-sulfonate (R)-7′: Butyl 1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropanesulfonate (S)-6: Butyl 1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}cyclopropanesulfonate (R)-6: Butyl 1-[(2S)-2,3-dihydroxypropyl]cyclopropanesulfonate (S)-5: Butyl 1-[(2R)-2,3-dihydroxypropyl]cyclopropanesulfonate (R)-5: Butyl 1-[(2S)-oxiran-2-ylmethyl]cyclopropanesulfonate (S)-4: Butyl 1-[(2R)-oxiran-2-ylmethyl]cyclopropanesulfonate (R)-4: Butyl 1-[(2S)-3-chloro-2-hydroxypropyl]cyclopropanesulfonate (S)-3: Butyl 1-[(2R)-3-chloro-2-hydroxypropyl]cyclopropanesulfonate (R)-3: Butyl 1-[(2S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-hydroxypropyl]cyclopropane-sulfonate (S)-9a: Butyl 1-[(2R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-hydroxypropyl]cyclopropane-sulfonate (R)-9a: Butyl 1-[(2S)-2-hydroxy-3-(tetrahydro-2H-pyran-2-yloxy)propyl]cyclopropane sulfonate (S)-9b:and
Butyl 1-[(2R)-2-hydroxy-3-(tetrahydro-2H-pyran-2-yloxy)propyl]cyclopropane sulfonate (R)-9b: