1: (4-bromo-phenyl)-acetic acid methyl ester With sodium hydride in N,N-dimethyl-formamide; mineral oil T=0°C; 0.25 h; 2: methyl iodide in N,N-dimethyl-formamide; mineral oil T=0 - 20°C; 12 h;

sulfuric acid; acetonitrile T=80 - 85°C; 16 - 18 h;

9,9-dimethyl-4,5-bis(diphenyl-phosphino)xanthene; bis(dibenzylideneacetone)-palladium(0) in tetrahydrofuran T=65°C; Reformatsky Reaction; 3 h; Inert atmosphereSealed tube; chemoselective reaction;

1: Methyl 2-(4'-bromophenyl)propanoate With n-butyllithium; diisopropylamine in tetrahydrofuran T=-78 - 0°C; 0.75 h; 2: methyl iodide in tetrahydrofuran T=-78 - 20°C; 1.5 h; 3: With potassium tert-butylate in tetrahydrofuran T=0 - 20°C; 1.5 h;

sulfuric acid Reflux; regioselective reaction;

1.1: AlCl3, aluminium chloride / Industry scale 2.1: sodium hydrogencarbonate; bromine / water / 13 h / 25 - 35 °C / Industry scale 2.2: 0 - 10 °C / pH 5 3.1: sulfuric acid / toluene / 16 h / 63 - 67 °C / Industry scale View Scheme

1.1: chloro-trimethyl-silane / tetrahydrofuran / 0.25 h / |Inert atmosphere; |Sealed tube 1.2: 57 °C / |Inert atmosphere; |Sealed tube 2.1: 9,9-dimethyl-4,5-bis(diphenyl-phosphino)xanthene; bis(dibenzylideneacetone)-palladium(0) / tetrahydrofuran / 3 h / 65 °C / |Inert atmosphere; |Sealed tube View Scheme

1: With water; lithium hydroxide hydrate in 1,4-dioxane T=50°C; 5.5 h; 2: With hydrogenchloride in 1,4-dioxane; water

hydrogenchloride in tetrahydrofuran

1: 97 percent / Et3N / tetrakis(triphenylphosphine)palladium(0), Cu2Br2 / 3.5 h / Heating 2: 100 percent / pyridine / CH2Cl2 / 20 h / Ambient temperature 3: 75 percent / K2CO3 / acetonitrile / 12 h / Heating 4: 75 percent / HgO, aq. H2SO4 / methanol / 3 h / 55 °C 5: 95 percent / NaBH4 / methanol / 20 h / Ambient temperature 6: 76 percent / aq. KOH / methanol / 16 h / 80 °C View Scheme