1: 1-bromo-2,4-dimethoxy-6-methylbenzene With n-butyllithium in tetrahydrofuran T=-78°C; 1 h; 2: methyl chloroformate in tetrahydrofuran T=-78 - 20°C;

1.1: n-BuLi / tetrahydrofuran / 1 h / -78 °C 1.2: 96 percent / tetrahydrofuran / -78 - 20 °C 2.1: 98 percent / AlCl3 / CH2Cl2 / 0 - 20 °C View Scheme

1: 1-bromo-2,4-dimethoxy-6-methylbenzene With n-butyllithium in tetrahydrofuran T=-78°C; metallation; 2: carbon dioxide T=-78 - 20°C; Carboxylation; Further stages.;

1: 1.) n-BuLi / 1.) Et2O, 0 deg, 30 min 2: (COCl)2 / 0 - 20 °C 3: pyridine 4: BBr3 / CH2Cl2 / 0.5 h / 0 °C 5: NaH / dimethylformamide 6: 1.) LDA / 1.) THF, -78 deg, 10 min 7: DDQ / dioxane / 0.17 h / 60 °C 8: K2CO3 / dimethylsulfoxide / 16 h / 20 °C 9: LAH / tetrahydrofuran / 1 h / 0 °C 10: pyridine / 24 h 11: imidazole / dimethylformamide / 16 h / 0 - 20 °C 12: TsOH / CH2Cl2; methanol / 0.08 h 13: 62 percent / PCC / CH2Cl2 / 20 °C 14: 91 percent / NBS / CH2Cl2 / 0.5 h / 20 °C 15: MCPBA, Na2SO4, 4,4'-methylenebis(2,6-di-t-butyl)phenol / benzene / 1 h / 20 °C 16: aq. NaOH / methanol; tetrahydrofuran / 20 °C 17: K2CO3 / dimethylsulfoxide / 16 h / 20 °C 18: TBAF 19: DEAD, PPh3 20: NaOH 22: 1.) t-BuLi, 2.) FeCl3 / 1.) THF, -78 deg, 2.) -78 deg to 20 deg 23: 1.) TBAF, 2.) H2 / 2.) Pd/C / 1.) THF, 2.) THF, MeOH 24: 65 percent / K3Fe(CN)6, NaOH / H2O; ethanol; tetrahydrofuran / 20 °C 25: 54 percent / DMAP, pyridine 26: aq. HCl View Scheme

1: 1.) n-BuLi / 1.) Et2O, 0 deg, 30 min 2: (COCl)2 / 0 - 20 °C 3: pyridine 4: BBr3 / CH2Cl2 / 0.5 h / 0 °C View Scheme

1.1: n-BuLi / tetrahydrofuran / 1 h / -78 °C 1.2: 96 percent / tetrahydrofuran / -78 - 20 °C 2.1: 98 percent / AlCl3 / CH2Cl2 / 0 - 20 °C 3.1: 72 percent / Ca(OH)2 / methanol / 72 h / 20 °C 4.1: 82 percent / KOH / methanol / 72 h / 20 °C View Scheme