Reaction Steps
tert-Butyl {3-[3-(5-(4-trifluoromethylphenoxy)-1H-pyrazol-3-yl)phenyl]oxetan-3-yl}carbamate (98 mg, 0.21 mmol), ethyl bromoacetate (80 mg, 0.47 nimbi), and potassium carbonate (67 mg, 0.48 mmol) were combined in 0.5 mL of DMF and the mixture was stirred at ambient temperature under argon atmosphere for 4 h, then warmed to 60° C. for 18 h. The mixture was diluted with EtOAc and washed with water and brine. The organic phase was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed on a 12 g silica gel column using 0-5% MeOH:CHCl3 over 16 min at 30 mL/min. The fractions containing the first-eluting product were combined and evaporated under reduced pressure to give ethyl [3-(4-trifluoromethylphenoxy)-5-(3-{3-[(tert-butyloxycarbonyl)amino]oxetan-3-yl}phenyl)-1H-pyrazol-1-yl]acetate (product A) as an oil, calcd (M+1)+: 562.6. Found: 562.2. 1H NMR (400 MHz, CDCl3) δ 7.6 (m, 5H), 7.50 (t, J=7, 1H), 7.37 (d, J=7, 1H), 7.29 (s, 1H), 5.99 (s, 1H), 5.85 (br s, 1H), 5.00 (d, J=5, 2H), 4.85 (br d, 2H), 4.79 (s, 2H), 4.21 (q, J=7, 2H), 1.27 (t, J=7, 3H). The fractions containing the second-eluting product were combined and evaporated under reduced pressure to give ethyl [5-(4-trifluoromethylphenoxy)-3-(3-{3-[(tert-butyloxycarbonyl)amino]oxetan-3-yl}phenyl)-1H-pyrazol-1-yl]acetate (product B) as an oil, calcd (M+1)+: 562.6. Found: 562.9. 1H NMR (400 MHz, CDCl3) δ 7.88 (br s, 1H), 7.6 (m, 3H), 7.50 (d, J=7, 1H), 7.42 (t, J=7, 1H), 7.32 (d, J=6, 2H), 6.03 (s, 1H), 5.82 (br s, 1H), 5.00 (br s, 2H), 4.90 (overlapping brs s and sharp s, 4H), 4.21 (q, J=7, 2H), 1.25 (t, J=7, 3H).
