1: carbonic acid chloromethyl ester isopropyl ester; (R)-9-[2-(phosphonomethoxy)propyl]adenine With chloro-trimethyl-silane; triethylamine; tetrabutylammomium bromide in 1-methyl-pyrrolidin-2-one T=50 - 55°C; 5 h; 2: (2E)-but-2-enedioic acid in isopropyl alcohol T=50°C;

in isopropyl alcohol T=0 - 45°C; 2.33333 h;

in isopropyl alcohol T=50°C;

1.1: Mg(O-t-Bu)2 / 1-methyl-pyrrolidin-2-one / 70 - 74 °C 2.1: chloro-trimethyl-silane; sodium bromide / 1-methyl-pyrrolidin-2-one / 0 - 75 °C 3.1: triethylamine / 1-methyl-pyrrolidin-2-one / 45 °C 3.2: 5.5 h / 45 - 50 °C 4.1: isopropyl alcohol / 2 h / 50 °C View Scheme

1.1: chloro-trimethyl-silane; sodium bromide / 1-methyl-pyrrolidin-2-one / 0 - 75 °C 2.1: triethylamine / 1-methyl-pyrrolidin-2-one / 45 °C 2.2: 5.5 h / 45 - 50 °C 3.1: isopropyl alcohol / 2 h / 50 °C View Scheme

1.1: triethylamine / 1-methyl-pyrrolidin-2-one / 45 °C 1.2: 5.5 h / 45 - 50 °C 2.1: isopropyl alcohol / 2 h / 50 °C View Scheme

1.1: sodium hydroxide / N,N-dimethyl-formamide / 120 °C 2.1: Mg(O-t-Bu)2 / 1-methyl-pyrrolidin-2-one / 70 - 74 °C 3.1: chloro-trimethyl-silane; sodium bromide / 1-methyl-pyrrolidin-2-one / 0 - 75 °C 4.1: triethylamine / 1-methyl-pyrrolidin-2-one / 45 °C 4.2: 5.5 h / 45 - 50 °C 5.1: isopropyl alcohol / 2 h / 50 °C View Scheme

1.1: chloro-trimethyl-silane; triethylamine; tetrabutylammomium bromide / N-methyl-pyrrolidine / 50 - 55 °C 1.2: 5 h / 50 - 55 °C 2.1: isopropyl alcohol / 50 °C View Scheme