Citric Acid → Tert-butyl 4-[2-(4-{[(tert-butoxycarbonyl)(1,3-thiazol-4-yl)amino]sulfonyl}-2-chloro-5-fluorophenoxy)-5-chlorophenyl]piperidine-1-carboxylate

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Reaction Steps

Example 655 from above can be made as follows. To a solution of tert-butyl 4-(5-chloro-2-hydroxyphenyl)piperidine-1-carboxylate (Preparation 231, 38 mg, 0.122 mmol) and potassium carbonate (50.6 mg, 0.366 mmol) in dimethyl sulfoxide (1 mL) was added tert-butyl [(5-chloro-2,4-difluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate (Preparation 453, 50 mg, 0.122 mmol). The mixture was stirred at room temperature for 16 hours before diluting with ethyl acetate (10 mL) and water (10 mL). The aqueous phase was acidified to pH 4 with saturated citric acid solution (aqueous) and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (30 mL), dried over sodium sulphate, filtered and concentrated in vacuo to afford tert-butyl 4-[2-(4-{[(tert-butoxycarbonyl)(1,3-thiazol-4-yl)amino]sulfonyl}-2-chloro-5-fluorophenoxy)-5-chlorophenyl]piperidine-1-carboxylate as a white foam. This was dissolved in dichloromethane (1 mL), trifluoroacetic acid added (200 μL) and reaction stirred for 16 hours at room temperature before concentrating in vacuo. Purification by preparative HPLC afforded the title compound.

Provenance & Evidence