反应详情

To a stirring solution of the product of Example 33, Step C, N-(2,2-dimethyl-[1,3]dioxan-5-yloxy)-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide (0.416 g, 0.980 mmol) in ethanol (5 mL) was added 1 molar aqueous hydrochloric acid solution (1 mL). After stirring for 1 hour at ambient temperature the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed twice with water and twice with brine. The organic layer was collected, dried over sodium sulfate, filtered and concentrated in vacuo. The affording foam was crystallized in ethyl acetate and heptane to afford 2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-N-(2-hydroxy-1-hydroxymethyl-ethoxy)-benzamide (0.318 g, 84.6%) as a white crystalline solid: m.p. 91-93° C.; 1 NMR (400 MHz; CD3OD) δ 7.38 (1 H, t, J=6.8 Hz), 6.85-6.96 (3 H, m), 6.73-6.78 (1 H, m), 3.86-3.82 (1 H), 3.64 (4 H, d, J=4.9 Hz), 2.58 (2 H, q, J=15.1, 7.6 Hz), 1.19 (3 H, t, J=7.6 Hz); 19F-NMR (376 MHz; CD3OD) δ −132.4, −134.6, −147.2; MS(APCI+)=385; Anal.calcd/found for C18H19F3N2O4: C, 56.25/56.38; H, 4.98/4.81; N, 7.29/7.25.

1. customwas partitioned between ethyl acetate and water
2. washThe organic layer was washed twice with water and twice with brine
3. customThe organic layer was collected
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe affording foam was crystallized in ethyl acetate