Pyridine → (R)-N-{2-Chloro-3-fluoro-4-[4-(N-methyl-N-ethylcarbamoyl)phenylsulphanyl]phenyl}-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

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Reaction Steps

2-Chloro3-fluoro-4-[4-(N-methyl-N-ethylcarbamoyl)phenylsulphanyl]aniline (Method 83; 580 mg, 1.7 mmol) was dissolved in DCM (6 ml) and pyridine (0.28 ml) was added. (S)-3,3,3-Trifluoro-2-(trimethylsilyloxy)-2-methylpropanoyl chloride (prepared from (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid (Method 25) as described in J. Med. Chem., 1999, 42, 2741-2746) (508 mg) was dissolved in DCM (1 ml) and added to the aniline. The solution was stirred for 4 hours and then washed with HCl (2 M) to remove excess pyridine. The organic layer was evaporated to dryness, dissolved in MeOH (17 ml) and HCl (2M, 1.7 ml) was added. The solution was left to stir overnight at room temp. The MeOH was removed and the residue was partitioned between water and EtOAc. The aqueous layer was extracted twice with EtOAc, the organic layers were combined, washed with water, brine and dried by pouring down a Chem Elut column and eluting with EtOAc. The resulting solution was evaporated to dryness and purified by chromatography on a Bond Elut column, eluting with 5-65% EtOAc/hexane to yield the title compound (390 mg) as a white solid. NMR: 1.0 (s, 3H), 1.6 (3, 3H), 2.8 (s, 3H), 3.2 (d, 2H), 7.2 (d, 2H), 7.3 (d, 2H), 7.6 (t, 1H), 7.9 (s, 1H), 9.9 (s, 1H); m/z 477.

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