6-Methoxy-2-(4-Methoxyphenyl)benzo[b]thiophene-3-Carboxylic Acid Chloride → Raloxifene Bismethyl Ether

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Reaction Steps

To a solution of 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene-3-carboxylic acid chloride (98.5 mg, 0.296 mmol) in tetrahydrofuran (3 ml) at 2° C. under nitrogen is added dropwise via syringe a solution of 4-[2-(1-piperidinyl)ethoxy]phenylmagnesium bromide (0.48 ml of 0.75 M solution, 0.36 mmol). The resulting mixture is stirred at that temperature for 16 hours, then quenched by addition of methyl alcohol. It is then partitioned between methylene chloride and saturated aqueous ammonium chloride, and the separated organic layer is dried over magnesium sulfate, filtered and concentrated to an oil, which is chromatographed on silica gel (10:5:1 hexanes:dichloromethane:triethylamine) to afford a product-containing fraction, which is further chromatographed on silica gel (10:1:1 hexanes:dichloromethane:triethylamine) to afford title compound as an oil: 88.4 mg (60%). 1H NMR spectrum identical to authentic sample. Anal. Calcd. for C30H31NO4S: C, 71.83; H, 6.23; N, 2.79; S, 6.39. Found: C, 71.59; H, 6.32; N, 2.69; S, 6.14.

Provenance & Evidence