(R)-N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionamide → (R)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-propionamide

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask was placed (R)—N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionamide (128 mg, 0.25 mmol), ethanol (10 mL) and concentrated hydrochloric acid (2 drops). This solution was then stirred at 25° C. until all starting material is consumed (˜1 hr). The reaction was then diluted with ethyl acetate (30 mL) and transferred to a separatory funnel where it was washed with a saturated aqueous solution of sodium bicarbonate (10 mL). The aqueous layer was then extracted with ethyl acetate (3×10 mL). The organic layers were then combined dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (4 g column, 20% ethyl acetate/hexanes to 60% ethyl acetate/hexanes) afforded (R)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-propionamide (89 mg, 90%) as a white foam: [α]30589=−22.2° (c=0.18, methylene chloride); ES-HRMS m/e calcd for C19H23N3O2Cl2 (M+H)+ 418.1059, observed 418.1061; 1H NMR (300 MHz, DMSO-d6) δ 1.10 (m, 2H, CH2), 1.35-1.79 (m, 8H, 4×CH2), 2.05 (m, 1H, CH), 3.67 (q, J=5.6 Hz, 2H, OCH2), 3.79 (m, 1H, ArCHCO), 4.00 (t, J=5.6 Hz, 2H, NCH2), 4.83 (t, J=5.4 Hz, 1H, OH), 6.40 (d, J=2.2 Hz, 1H, Ar), 7.34 (dd, Jm=2.0 Hz, Jo=8.2 Hz, 1H, Ar), 7.53 (d, J=2.2 Hz, 1H, Ar), 7.58 (d, Jo=8.2 Hz, 1H, Ar), 7.59 (s, 1H, Ar), 10.71 (s, 1H, NH).

Provenance & Evidence