7-chloro-4-methoxy-1H-indole

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-chloro-4-(methyloxy)-1H-indole (D11) (1.15 g, 6.35 mmol) in dichloromethane (20 mL) was added 3-fluoro-4-methoxyphenylboronic acid (2.2 g, 12.9 mmol), triethylamine (1.8 mL, 12.9 mmol), copper (II) acetate (2.3 g, 12.7 mmol) and powdered 4A molecular sieves (2.0 g). The reaction mixture was stirred at room temperature in the presence of air for 3 days. Further quantities of 3-fluoro-4-methoxyphenylboronic acid (440 mg), triethylamine (0.36 mL) and copper acetate (440 mg) were added and the mixture stirred at room temperature in the presence of air for a further 16 hours. The mixture was filtered and the solid washed with dichloromethane. The filtrate was concentrated at reduced pressure. The product was partially purified by silica gel chromatography eluting with 2-35% dichloromethane in hexane. The resulting product was partially dissolved in dimethylsulphoxide and acetonitrile. The undissolved solid was collected by filtration to yield the title compound (D12) (440 mg). The filtrate was concentrated at reduced pressure and the product purified by MDAP to yield a further batch of the title compound (D12), (143 mg). the mixture stirred at room temperature in the presence of air for a further 16 hours The mixture was filtered the solid washed with dichloromethane The filtrate was concentrated at reduced pressure The product was partially purified by silica gel chromatography eluting with 2-35% dichloromethane in hexane The resulting product was partially dissolved in dimethylsulphoxide The undissolved solid was collected by filtration

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-chloro-3-nitroanisole (6.0 g, 32.0 mmol) in tetrahydrofuran (140 mL) at −40° C. was added vinylmagnesium bromide (1M in tetrahydrofuran, 112 mL, 112.0 mmol). The mixture was stirred at −40° C. for 1.5 hours and then quenched by the addition of saturated aqueous ammonium chloride solution (150 mL). The reaction mixture was allowed to warm to room temperature and then the product extracted into ethyl acetate (×2). The combined organic layers were dried over magnesium sulphate, filtered and concentrated at reduced pressure. The product was purified by silica gel chromatography eluting with 2-15% ethyl acetate in hexane to yield the title compound (D11), (1.67 g). quenched by the addition of saturated aqueous ammonium chloride solution (150 mL) to warm to room temperature the product extracted into ethyl acetate (×2) The combined organic layers were dried over magnesium sulphate filtered concentrated at reduced pressure The product was purified by silica gel chromatography eluting with 2-15% ethyl acetate in hexane