MgCl2*6H2O; palladium 10 on activated carbon; hydrogen in tetrahydrofuran; water T=26 - 38°C; P=3750.38 Torr; 2 h; Large scale;

1: With N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide T=-40 - 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=25°C; pH=6.5 - 7.0; 3 h;

N-ethyl-aniline; tetrakis(triphenylphosphine) palladium(0) in tetrahydrofuran; water; isopropyl alcohol T=25°C; 4.5 h; Product distribution / selectivity;

1: 4-nitrobenzyl-4-(acetylsulfanyl)-2-{[(tert-butoxycarbonyl)(sulfamoyl)amino]methyl}pyrrolidine-1-carboxylate With acetyl chloride in methanol 3 h; Reflux; 2: 4-nitrobenzyl (4R)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate With N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide T=-35 - 25°C; 3: With 4-methyl-morpholine; 2.5 wt Pd/C; hydrogen; acetic acid in water; N,N-dimethyl-formamide T=10 - 25°C; P=3000.3 - 4500.45 Torr; pH=5.8 - 6.5;

aluminium trichloride; methoxybenzene in dichloromethane T=-30°C; 1.5 h;

aluminium trichloride; methoxybenzene in dichloromethane T=-30°C; 1.5 h;

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; MgCl2*6H2O / water; tetrahydrofuran / 25 - 35 °C / 3750.38 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; MgCl2*6H2O / water; tetrahydrofuran / 25 - 35 °C / 3750.38 Torr View Scheme

1: 96 percent / NaOH / methanol / 3 h / Ambient temperature 2: 1.) ethyl chloroformate, triethylamine, 2.) sodium borohydride, tetra-n-butylammonium bromide / 1.) CH2Cl2, -40 deg C, 40 min, 2.) water, CH2Cl2, -10 deg C, 1 h 3: 86 percent / dimethylformamide / 3.75 h / 65 °C 4: triphenylphosphine, diethyl azodicarboxylate / tetrahydrofuran / 4 h / Ambient temperature 5: 69 percent / sodium methoxide / methanol / 0.5 h / -35 °C 6: 87 percent / diisopropylethylamine / 4.5 h 7: 72 percent / AlCl3, anisole / CH2Cl2 / 1.5 h / -30 °C View Scheme

1: 1.) ethyl chloroformate, triethylamine, 2.) sodium borohydride, tetra-n-butylammonium bromide / 1.) CH2Cl2, -40 deg C, 40 min, 2.) water, CH2Cl2, -10 deg C, 1 h 2: 86 percent / dimethylformamide / 3.75 h / 65 °C 3: triphenylphosphine, diethyl azodicarboxylate / tetrahydrofuran / 4 h / Ambient temperature 4: 69 percent / sodium methoxide / methanol / 0.5 h / -35 °C 5: 87 percent / diisopropylethylamine / 4.5 h 6: 72 percent / AlCl3, anisole / CH2Cl2 / 1.5 h / -30 °C View Scheme