Sulfonamide (coupling amine and sulfonyl chloride):

 

To a solution of ((R)-5-amino-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid tert- butyl ester hydrochloride salt (1.04 g, 3.30 mmol) and DIEA (1.36 ml, 7.86 mmol) in dry tetrahydrofuran (15 ml) was added 3-fluoro-5- (thfluoromethyl)-benzenesulfonyl chloride (0.867 g, 3.30 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight, and then concentrated. The remaining residue was partitioned between water and ethyl acetate. The collected organic layers were washed with water, dried over magnesium sulfate, filtered, and evaporated in vacuo. Flash chromatography (RediSep® Flash column from Teledyne Isco, Inc., 230-400 mesh, 0-10% ethyl acetate in hexane) gave [(R)-5-(3-fluoro-5-trifluoromethyl-benzenesulfonylamino)- 5,6,7,8-tetrahydro-naphthalen-1 -yloxy]-acetic acid tert-butyl ester (867 mg, 52%). 

 

Patent reference: WO2010018112 (Roche)

 

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