trans-N,N'-dimethylcyclohexane-1,2-diamine; potassium phosphate; copper(l) iodide in toluene T=120°C; 24 h; Inert atmosphere;

1: (S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol methanesulfonate With sodium carbonate in n-heptane; water; ethyl acetate T=15°C; pH=7.2; 0.333333 h; 2: phosgene T=12 - 20°C; 1.5 h; Product distribution / selectivity;

sodium carbonate in n-heptane; water; ethyl acetate T=5 - 15°C; 1 h; Product distribution / selectivity;

1: (S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol methanesulfonate With sodium carbonate in n-heptane; water; ethyl acetate T=15°C; pH=6.1; 0.333333 h; 2: bis(trichloromethyl) carbonate T=12°C; 1 h; Product distribution / selectivity;

1: (S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol methanesulfonate With sodium carbonate in n-heptane; water; ethyl acetate T=15°C; 0.0833333 h; 2: trichloromethyl chloroformate T=12°C; 1.5 h; Product distribution / selectivity;

1.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / -78 °C 1.2: 2.5 h / 0 °C 2.1: dimethyl zinc / naphthalene-1-sulfonic acid ((R)-2-hydroxy-1-methyl-2,2-diphenyl-ethyl)-amide / n-heptane; toluene / 1.5 h / 20 °C / Inert atmosphere 2.2: 20 h / 20 °C 3.1: ethyl acetate / 1.5 h / 0 - 20 °C 3.2: 18 h / 0 - 20 °C 4.1: potassium phosphate; trans-N,N'-dimethylcyclohexane-1,2-diamine / copper(l) iodide / toluene / 24 h / 120 °C / Inert atmosphere View Scheme

1.1: ethyl acetate / 1.5 h / 0 - 20 °C 1.2: 18 h / 0 - 20 °C 2.1: potassium phosphate; trans-N,N'-dimethylcyclohexane-1,2-diamine / copper(l) iodide / toluene / 24 h / 120 °C / Inert atmosphere View Scheme

1.1: dimethyl zinc / naphthalene-1-sulfonic acid ((R)-2-hydroxy-1-methyl-2,2-diphenyl-ethyl)-amide / n-heptane; toluene / 1.5 h / 20 °C / Inert atmosphere 1.2: 20 h / 20 °C 2.1: ethyl acetate / 1.5 h / 0 - 20 °C 2.2: 18 h / 0 - 20 °C 3.1: potassium phosphate; trans-N,N'-dimethylcyclohexane-1,2-diamine / copper(l) iodide / toluene / 24 h / 120 °C / Inert atmosphere View Scheme

1.1: diethylzinc; N-pyrrolidinylnorephedrine / toluene; tetrahydrofuran / 1.5 h / 15 - 20 °C 1.2: 20 - 30 °C 2.1: sodium carbonate / ethyl acetate; n-heptane; water / 1 h / 5 - 15 °C View Scheme

1.1: diethylzinc; N-pyrrolidinylnorephedrine / toluene; tetrahydrofuran / 1.5 h / 15 - 20 °C 1.2: 20 - 30 °C 2.1: sodium carbonate / ethyl acetate; n-heptane; water / 1 h / 5 - 15 °C View Scheme