Acetic Acid → HCID 86684786, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of Methyl 4-[(2R,4S)-1-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-4-{[(1,1-dimethylethyl)sulfinyl]amino}-2-(4-fluoro-2-methylphenyl)-4-piperidinyl]-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2-butenoate (Intermediate 10, 184 mg, 0.220 mmol) and Acetic acid (0.025 mL, 0.439 mmol) in Acetonitrile (4 mL) was added Cesium Fluoride (107 mg, 0.703 mmol, Aldrich) and the reaction mixture was stirred at 25° C. for 5 hrs. NaHCO3 saturated solution was added very carefully and the mixture was extracted with EtOAc (3×). The combined organic phases were dried (Na2SO4) and evaporated to dryness. The crude was purified by flash chromatography on silica with SP1 (Biotage) system (from 1:0 to 0:1 Cyclohexane/EtOAc) to give the title compound (108 mg, 0.149 mmol, 68% yield) as a colourless oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.92-8.03 (m, 1H) 7.62-7.75 (m, 2H) 6.68-7.30 (m, 3H) 5.20-5.37 (m, 1H) 4.94-5.07 (m, 1H) 4.30-4.46 (m, 1H) 3.67-3.81 (m, 3H) 2.86-3.07 (m, 2H) 1.58-2.77 (m, 14H) 1.45-1.53 (m, 3H) 1.03-1.12 (m, 9H). Mixture of two species (see the signals of OMe at 3.77 ppm, 3.70 ppm). UPLC: 2 peaks Rt 0.87 and 0.93 mins, m/z=724 [M+H]+.

Provenance & Evidence