Triethylamine → 4-[4-(4-Fluorophenoxy)benzenesulfonylamino]tetrahydropyran-4-carboxylic acid ethyl ester

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Reaction Steps

To a solution of 4-aminotetrahydropyran-4-carboxylic acid ethyl ester (7.00 grams, 0.0404 mole) in N,N-dimethylformamide (40 mL) was added triethylamine (5.94 mL, 0.043 mole). Solid 4-(4-fluorophenoxy)benzenesulfonyl chloride (12.165 grams, 0.0424 mole) was added in portions. The resulting mixture was stirred at room temperature for 16 hours and then most of the solvent was removed by evaporation under vacuum. The residue was partitioned between saturated sodium bicarbonate solution and dichloromethane. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine and dried over sodium sulfate. Evaporation of the solvent under vacuum provided crude 4-[4-(4-fluorophenoxy)benzenesulfonylamino]tetrahydropyran-4-carboxylic acid ethyl ester as an amber oil (21.05 grams). Flash chromatography on silica gel eluting with 25% ethyl acetate/hexane followed by 50% ethyl acetate/hexane provided 4-[4-(4-fluorophenoxy)benzenesulfonylamino]tetrahydropyran-4-carboxylic acid ethyl ester as an off-white crystalline solid (12.15 grams, 71%, mp 116-117° C.).

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