1: (1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl- carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester With palladium 10 on activated carbon; hydrogen in isopropyl alcohol T=20°C; P=760.051 Torr; 2: (2E)-but-2-enedioic acid in ethanol

1: (1S,2S,4S)-4-(2-carbamoyl-2-methylpropylcarbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl carbamic acid tert-butyl ester With hydrogenchloride in dichloromethane T=0°C; 3 h; 2: (2E)-but-2-enedioic acid in ethanol

in methanol SolventConcentrationTimeTemperature;

1: 5(S)-amino-4(S)-hydroxy-2(S),7(S)-diisopropyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid [N-(2-carbamoyl-2,2-dimethyl-ethyl)]-amide hydrochloride With sodium hydroxide in water T=0°C; 2: (2E)-but-2-enedioic acid in methanol

1: (2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide With hydrogen; ethanolamine; 5 palladium on charcoal in ethanol P=2206.72 Torr; 2: (2E)-but-2-enedioic acid in ethanol Product distribution / selectivity;

1: triethylamine; 2-hydroxy-pyridine / 16 h / 85 - 90 °C 2: hydrogen; ethanolamine / palladium 10 on activated carbon / isopropyl alcohol / 3 h 3: ethanol / 0.17 h / 25 - 30 °C View Scheme

1.1: 4-(N,N-dimethlyamino)pyridine / anhydrous dichloroethane / 0.5 h / 20 °C 1.2: 14.5 h / 10 - 30 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -70 °C / Inert atmosphere 2.2: -70 - 5 °C 3.1: dihydrogen peroxide; lithium hydroxide hydrate / water; tetrahydrofuran / 0 - 30 °C 4.1: sodium tetrahydroborate / tetrahydrofuran / 1 h / 0 - 5 °C / Inert atmosphere 4.2: 5.75 h / 0 - 30 °C 5.1: N-chloro-succinimide; triphenylphosphine / dichloromethane / 5.5 h / -40 - 30 °C 6.1: magnesium; ethylene dibromide / tetrahydrofuran / 4.17 h / 63 - 68 °C / Inert atmosphere 6.2: 12.5 h / 0 - 5 °C 7.1: water; lithium hydroxide hydrate / tetrahydrofuran; methanol / 26 h / 65 - 70 °C 7.2: 0.5 h / 0 - 5 °C 8.1: hydrogenchloride / anhydrous dichloroethane; water / 0 - 5 °C / pH 2.5 8.2: 14.25 h / 0 - 30 °C 9.1: N-bromosuccinmide; phosphoric acid / water; tetrahydrofuran / 1.25 h / 0 - 5 °C 10.1: sodium azide / ethylene glycol / 20 h / 80 - 85 °C 11.1: triethylamine; 2-hydroxy-pyridine / 16 h / 85 - 90 °C 12.1: hydrogen; ethanolamine / palladium 10 on activated carbon / isopropyl alcohol / 3 h 13.1: ethanol / 0.17 h / 25 - 30 °C View Scheme

1: triethylamine; 2-hydroxy-pyridine / 30 h / 80 - 90 °C 2: sodium hydroxide; dihydrogen peroxide / water / 20 - 40 °C 3: hydrogen; ethanolamine / 5 palladium on charcoal / ethanol / 2206.72 Torr View Scheme

1: hydrogen; ammonia / raney nickel / methanol / 14 h / 40 - 45 °C / 2942.29 Torr 2: triethylamine; 2-hydroxy-pyridine / 16 h / 85 - 90 °C 3: hydrogen; ethanolamine / palladium 10 on activated carbon / isopropyl alcohol / 3 h 4: ethanol / 0.17 h / 25 - 30 °C View Scheme

in ethanol T=40°C; Product distribution / selectivity;