Hydrochloric Acid → HCID 178461688, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled (−30° C.) solution of the intermediate 7a, methyl (4R)-3-oxo-4-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)pentanoate, (372 mg, 1 mmol) in CH3OH (0.5 ml), a solution of NaOH (42 mg, 1.05 mmol) in CH3OH (4 ml) was added by dripping. The resulting mixture was stirred for 10 min, then a mixture of hydroxylamine hydrochloride (133 mg, 2 mmol) and NaOH (83 mg, 2 mmol) in CH3OH/water (4 ml/0.5 ml) was added at the same temperature. After stirring for 2 h at −30° C., the reaction mixture was poured into 37% HCl (1.5 ml) and the resulting mixture was heated at 80° C. for 2 h. After cooling at room temperature and solvents evaporation, the crude was diluted with water and extracted with EtOAc (3×10 ml). The combined organic extracts were dried over anhydrous Na2SO4, evaporated and purified by flash chromatography (n-hexane/EtOAc 8:2; 1% AcOH) to afford pure 5-[(1R)-1-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)ethyl]isoxazol-3-ol (10) (202 mg, 0.57 mmol) as a pale yellow solid (57%). [α]D=−40 (c=1.4; CH3OH); 1H-NMR (CDCl3): δ 10.70 (bs, 1H, OH), 9.15 (bs, 1H, NH), 7.40 (d, 2H, J=7 Hz), 7.25 (d, 2H, J=7 Hz), 7.00 (s, 1H), 5.70 (s, 1H), 3.80 (q, 1H, J=7 Hz), 1.55 (d, 3H, J=7 Hz).

Provenance & Evidence