2,6-dimethylpyridine; hydrogen; 10percent Pa/C in tetrahydrofuran; water P=13501.4 Torr; 1 h;

1: With N-ethyl-N,N-diisopropylamine in 1-methyl-pyrrolidin-2-one; water T=-20 - -5°C; 2: With 4-methyl-morpholine; hydrogenchloride; 5 Pd(II)/C(eggshell); hydrogen in 1-methyl-pyrrolidin-2-one; water T=25°C; pH=6.5 - 7;

1: With N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide T=-50 - 25°C; 1 h; 2: With 4-methyl-morpholine; hydrogen; acetic acid; palladium on activated carbon in water; ethyl acetate; N,N-dimethyl-formamide T=20 - 25°C; pH=~ 7; 3 h;

4-methyl-morpholine; hydrogen; acetic acid in water; ethyl acetate T=20 - 25°C; pH=~ 7; 3 h; Aqueous buffer; Product distribution / selectivity;

1: dirhodium(II) tetraoctanoate / dichloromethane / 7 h / Reflux 2: N-ethyl-N,N-diisopropylamine / 4-(N,N-dimethlyamino)pyridine / dichloromethane / -35 °C 3: N-ethyl-N,N-diisopropylamine / dichloromethane / -35 - -30 °C 4: hydrogen; 2,6-dimethylpyridine / palladium 10 on activated carbon / water; tetrahydrofuran / 20 - 25 °C / 13501.4 Torr View Scheme

1: N-ethyl-N,N-diisopropylamine / 4-(N,N-dimethlyamino)pyridine / dichloromethane / -35 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / -35 - -30 °C 3: hydrogen; 2,6-dimethylpyridine / palladium 10 on activated carbon / water; tetrahydrofuran / 20 - 25 °C / 13501.4 Torr View Scheme

1.1: triethylamine; isopropyloxycarbonylchloride / dichloromethane / -30 - -20 °C 2.1: triethylamine / dichloromethane / -20 °C 3.1: N,N-dimethyl-formamide / 70 - 80 °C 4.1: sodium hydroxide; water / methanol / 5 - 10 °C 4.2: pH 2 5.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / -25 °C 6.1: hydrogen / palladium on activated charcoal / ethyl acetate; water / 3-(N-morpholino)propanesulfonic acid buffer View Scheme

1.1: sodium hydroxide / water / 0 - 5 °C 1.2: 0 - 5 °C 1.3: 0 - 5 °C 2.1: triethylamine; isopropyloxycarbonylchloride / dichloromethane / -30 - -20 °C 3.1: triethylamine / dichloromethane / -20 °C 4.1: N,N-dimethyl-formamide / 70 - 80 °C 5.1: sodium hydroxide; water / methanol / 5 - 10 °C 5.2: pH 2 6.1: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / -25 °C 7.1: hydrogen / palladium on activated charcoal / ethyl acetate; water / 3-(N-morpholino)propanesulfonic acid buffer View Scheme

1: hydrogenchloride; water / ethyl acetate 2: triethylamine / ethyl acetate; toluene 3: dirhodium(II) tetraoctanoate / acetone / Reflux 4: N-ethyl-N,N-diisopropylamine; zinc(II) iodide / acetone / -30 °C 5: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / -25 °C 6: hydrogen / palladium on activated charcoal / ethyl acetate; water / 3-(N-morpholino)propanesulfonic acid buffer View Scheme

1: 1,1'-carbonyldiimidazole / acetonitrile 2: hydrogenchloride; water / ethyl acetate 3: triethylamine / ethyl acetate; toluene 4: dirhodium(II) tetraoctanoate / acetone / Reflux 5: N-ethyl-N,N-diisopropylamine; zinc(II) iodide / acetone / -30 °C 6: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / -25 °C 7: hydrogen / palladium on activated charcoal / ethyl acetate; water / 3-(N-morpholino)propanesulfonic acid buffer View Scheme