Toluene-4-sulfonic acid 2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethyl ester → 3-{4-[2-(1-Benzyl-3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-(2-fluoro-phenoxy)-2-methyl-propionic acid

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Reaction Steps

2-(2-Fluoro-phenoxy)-3-(4-{2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-propionic acid ethyl ester Cesium carbonate (6.12 g, 18.76 nmol) is added to a solution of 2-(2-Fluoro-phenoxy)-3-(4-hydroxy-phenyl)-2-methyl-propionic acid ethyl ester 1.99 g, 6.26 mmol) and toluene-4-sulfonic acid 2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethyl ester (2.88 g, 6.88 mmol) in DMF (20 mL). The resultant mixture is stirred at 65° C. under an atmosphere of nitrogen for 18 h, then diluted with ethyl acetate. The organic layer is washed with 1N HCl, water, and brine. The organic layer is dried over MgSO4, concentrated in vacuo, and purified by flash column chromatography (17% acetone in hexanes) to provide the title compound (3.4 g, 97%). 1H NMR (400 MHz, CDCl3): δ 7.19 (d, 2H, J=5.4 Hz), 7.17 (d, 2H, J=5.4 Hz), 7.07-7.01 (m, 1H), 6.97-6.87 (m, 3H), 6.83 (d, 2H, J=8.6 Hz), 6.74 (d, 2H, J=8.6 Hz), 4.32, 4.28 (ABq, 2H, J=14.6 Hz), 4.20 (q, 2H, J=7.5 Hz), 3.94 (t, 2H, J=5.9 Hz), 3.77 (s, 3H), 3.60-3.53 (m, 1H), 3.33 (t, 1H, J=8.6 Hz), 3.26, 3.14 (ABq, 2H, J=14.0 Hz), 2.92 (t, 1 h, J=8.6 Hz), 2.82 (s, 3H), 2.24-2.17 (m, 1H), 1.89-1.82 (m, 1H), 1.38 (s, 3H), 1.23 (t, 3H, J=7.5 Hz). MS [EI+] 565 (M+H)+. Rf=0.48 in 50% acetone in hexanes.

Provenance & Evidence