反应详情

The title compound was prepared from the reaction of the product of Step D, 2-[(4-ethyl-2-fluorophenyl)amino]-3,4-difluorobenzoic acid (93 mg, 0.32 mmol) dissolved in dry THF (5 mL), and carbonyldiimidazole (CDI) (102 mg, 0.63 mmol). Within 10 minutes, a bright yellow solution was obtained and conversion to the imidazolide was confirmed by TLC (50% EtOAc/hexanes). A solution of 2-(aminooxy)ethanol (97 mg, 1.26 mmol) in THF (5 mL) was then added and the mixture stirred for 15 hours at room temperature. The reaction solvent was removed under reduced pressure and the residue partitioned between 1 M HCl (50 mL) and EtOAc (50 mL). The EtOAc layer was then washed with water (50 mL) and saturated NaCl solution (50 mL), dried (Na2SO4), and the solvent removed under reduced pressure to afford an oil which was purified by flash column chromatography on silica gel (50% EtOAc/hexanes) to give 2-[(4-ethyl-2-fluorophenyl)amino]-3,4-difluoro-N-(2-hydroxyethoxy)benzamide as a cream solid (65%); m.p. (EtOAc/hexanes) 134-138° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.84 (br s, 1 H), 8.76 (br s, 1 H), 7.43-7.37 (m, 1 H), 7.14-7.02 (m, 2 H), 6.90 (dd, J=8.3, 1.5 Hz, 1 H), 6.83 (td, J=8.6, 4.4 Hz, 1 H), 4.70 (br s, 1 H), 3.86 (t, J=4.9 Hz, 2 H), 3.57 (t, J=4.9 Hz, 2 H), 2.54 (q, J=7.6 Hz, 2 H), 1.15 (t, J=7.6 Hz, 3 H).

1. customa bright yellow solution was obtained
2. customThe reaction solvent was removed under reduced pressure
3. customthe residue partitioned between 1 M HCl (50 mL) and EtOAc (50 mL)
4. washThe EtOAc layer was then washed with water (50 mL) and saturated NaCl solution (50 mL)
5. dry with materialdried (Na2SO4)
6. customthe solvent removed under reduced pressure
7. customto afford an oil which
8. customwas purified by flash column chromatography on silica gel (50% EtOAc/hexanes)