in n-heptane; toluene Product distribution / selectivity;

1: (1-{(R)-1-{3-[(E)-2-(7-chloro-quinolin-2-yl)vinyl]phenyl}-3-[2-(1-methyl-1-trimethylsilanyloxyethyl)phenyl]propylsulfanylmethyl}cyclopropyl)acetic acid methyl ester With water; sodium hydroxide in 2-methyl tetrahydrofuran; methanol T=70 - 80°C; 2 h; Inert atmosphere; 2: N,N-dicyclohexylamine in hexane; ethyl acetate T=20°C;

1: 1-(mercaptomethyl)-cyclopropaneacetic acid With sodium hydride in N,N-dimethyl-formamide T=-5°C; 1 h; 2: 2-[2-[(3S)-[3-[(2E)-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-chloropropyl]phenyl]-2-propanol in N,N-dimethyl-formamide T=-5 - 0°C; 13 h; 3: N,N-dicyclohexylamine in ethyl acetate T=20 - 22°C; 1.75 h;

1: 1-(mercaptomethyl)cyclopropane acetic acid dilithium salt; 2-(2-(3(S)-(3-(2-(7-chloro-2-quinolinyl)-ethenyl)phenyl)-3-hydroxypropyl)phenyl)-2-propanol methanesulfonate in tetrahydrofuran; hexanes T=-5°C; 8.5 h; 2: N,N-dicyclohexylamine in tetrahydrofuran; hexanes; ethyl acetate T=20°C; 1 h;

1: [R,E]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[(2-hydroxypropan-2-yl)phenyl]propyl]thio] methyl]-cyclopropane acetic acid methyl ester With sodium hydroxide; water in water; toluene T=40 - 50°C; 15 h; 2: N,N-dicyclohexylamine in acetone T=25 - 35°C; 10 h; Product distribution / selectivity;

1: 2-(1-((((R)-1-(3-((E)-2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-(2-(2-hydroxypropan-2-yl)phenyl)propyl)sulfanyl)methyl)cyclopropyl)acetonitrile With sodium hydroxide; water in toluene T=125°C; 15 h; 2: N,N-dicyclohexylamine in acetone T=25 - 35°C; 10 h; Product distribution / selectivity;

1: 1-(mercaptomethyl)-cyclopropaneacetic acid With sodium methylate in methanol; dimethyl sulfoxide T=-5 - 0°C; 1 h; 2: (S)-benzenepropanol α-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-2-(1-hydroxy-1-methyl ethyl)-α-methane sulfonate in methanol; water; dimethyl sulfoxide T=-5 - 20°C; 10.5 h; 3: N,N-dicyclohexylamine With sodium hydroxide; acetic acid Product distribution / selectivity; more than 3 stages;

1: 1-(mercaptomethyl)-cyclopropaneacetic acid With n-butyllithium in tetrahydrofuran T=-12.5°C; 0.666667 h; 2: 2-(3-(S)-(3-(2-(7-chloroquinolinyl)ethenyl)phenyl)-3-methanesulfonyloxypropyl)phenyl-2-propanol in tetrahydrofuran T=-2°C; 3.5 h; 3: N,N-dicyclohexylamine in isopropyl alcohol; acetonitrile T=29°C; 15.5 h; Product distribution / selectivity;

1.1: sodium acetate; tetrabutylammomium bromide / palladium diacetate / toluene; 1-methyl-pyrrolidin-2-one / 120 °C / Inert atmosphere 2.1: 1H-imidazole / tetrahydrofuran / 20 °C 3.1: benzo[1,3,2]dioxaborole; (R)-(+)-o-tolyl-CBS-oxazaborolidine / dichloromethane / -50 - -40 °C / Inert atmosphere 4.1: triethylamine / dichloromethane / 0.5 h / 0 - 5 °C 5.1: 1-methyl-pyrrolidin-2-one / 0 - 20 °C / Inert atmosphere 6.1: sodium hydroxide; water / 2-methyl tetrahydrofuran; methanol / 2 h / 70 - 80 °C / Inert atmosphere 6.2: 20 °C View Scheme

1.1: sodium acetate; tetrabutylammomium bromide / palladium diacetate / toluene; 1-methyl-pyrrolidin-2-one / 120 °C / Inert atmosphere 2.1: 1H-imidazole / tetrahydrofuran / 20 °C 3.1: benzo[1,3,2]dioxaborole; (R)-(+)-o-tolyl-CBS-oxazaborolidine / dichloromethane / -50 - -40 °C / Inert atmosphere 4.1: triethylamine / dichloromethane / 0.5 h / 0 - 5 °C 5.1: 1-methyl-pyrrolidin-2-one / 0 - 20 °C / Inert atmosphere 6.1: sodium hydroxide; water / 2-methyl tetrahydrofuran; methanol / 2 h / 70 - 80 °C / Inert atmosphere 6.2: 20 °C View Scheme