Hydrochloric Acid → 3-cyclopentyl-2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-N-thiazol-2-yl-propionamide

Temperature

25 °C

A solution of benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (188 mg, 0.42 mmol) and 3-cyclopentyl-2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-propionic acid (94 mg, 0.28 mmol) in N,N-dimethylformamide (5 mL) was treated with N,N-diisopropylethylamine (150 μL, 0.85 mmol) and 2-aminothiazole (42.5 mg, 0.42 mmol). The mixture was stirred at 25° C. for 48 h. At this time, the reaction mixture was poured into cold water (25 mL) containing a 1N aqueous hydrochloric acid solution (50 mL) and extracted into ethyl acetate (2×75 mL) and diethyl ether (1×25 mL). The combined organic layers were then washed with water (2×75 mL) and a saturated aqueous sodium chloride solution (3×75 mL), dried over magnesium sulfate and sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-N-thiazol-2-yl-propionamide (50.5 mg, 43.1%) as a clear oil: FAB-HRMS m/e calcd for C19H21F3N2OS2 (M+H)+ 415.1125, found 415.1123.

1. extractionextracted into ethyl acetate (2×75 mL) and diethyl ether (1×25 mL)
2. washThe combined organic layers were then washed with water (2×75 mL)
3. dry with materiala saturated aqueous sodium chloride solution (3×75 mL), dried over magnesium sulfate and sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo

ORD record

ord-99669fc9dd094ac68a9ffaaa41d8fc59

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06610846B1