pig liver esterase; sodium hydroxide T=23°C; 30 h; aq. phosphate bufferResolution of racemateLarge scale reactionEnzymatic reaction; optical yield given as percent eeenantioselective reaction;

4-(N,N-dimethlyamino)pyridine; (R)-N-(tert-butoxycarbonyl)proline; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride in 1,2-dichloro-ethane T=0 - 20°C;

1: pyridine / 3 h / 20 °C / |Inert atmosphere 2: N,N-dimethyl-formamide / 12 h / 100 °C / |Inert atmosphere 3: sodium methylate / methanol / 4 h / 0 - 20 °C / |Inert atmosphere View Scheme

1.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 1.2: Reflux 2.1: 4-(N,N-dimethlyamino)pyridine / N,N-dimethyl-formamide / 20 °C 3.1: sodium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct / N,N-dimethyl-formamide / 90 °C 4.1: water; lithium hydroxide hydrate / tetrahydrofuran / 20 °C 4.2: pH 5 5.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.5 h / 20 °C 5.2: 0.5 h / 20 °C 6.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C View Scheme

1: (1R)-1-(2,6-dichloro-3-fluorophenyl)ethanol With sodium hydride in tetrahydrofuran; mineral oil T=0 - 20°C; 2.5 h; 2: 2-nitro-3-fluoropyridine in tetrahydrofuran; mineral oil T=0 - 20°C; 3.3 h;

1: With triphenylphosphine in tetrahydrofuran T=20°C; 1 h; 2: With di-isopropyl azodicarboxylate in tetrahydrofuran T=0°C; 12 h;