反应详情

3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (1.00 g, 2.21 mmol) was dissolved in dry dimethoxyethane (DME, 18 ml) under a nitrogen atmosphere, Pd(Ph3P)4 (0.13 g, 0.11 mmol) was added and the resulting yellow solution was stirred at ambient temperature for 20 min. K2CO3 (−325 mesh, 0.31 g, 2.21 mmol), water (5.3 ml) and boron complex 2 (0.54 g, 2.21 mmol) were added and the contents of the flask were refluxed for 1 h.1 Water (50 ml) and brine (50 ml) were added and the aqueous phase was extracted with ethyl acetate (3×50 ml). The combined organic extracts were washed with brine (20 ml) and dried over MgSO4. The solvent was removed under vacuum and the residual dark orange oil was chromatographed (ethyl acetate as eluent) to give 0.59 g (76% yield) of 2-[(4-vinyl-2-fluorophenyl)amino]-3,4-difluoro-N-(2-hydroxy-ethoxy)benzamide as a light yellow solid, mp 134–137° C. 1H NMR (d6-DMSO) δ 3.53–3.54 (m, 2 H), 3.82 (s, 2 H), 4.69–4.72 (m, 1 H), 5.14 (d, 1H, J=11 Hz), 5.69–5.77 (m, 1 H), 6.57–6.64 (m, 1 H), 6.77–6.83 (m, 1 H), 7.09–7.18 (m, 2 H), 7.33–7.40 (m, 2 H), 8.74 (bs, 1 H), 11.86 (bs, 1 H).

1. temperaturethe contents of the flask were refluxed for 1 h
2. extractionthe aqueous phase was extracted with ethyl acetate (3×50 ml)
3. washThe combined organic extracts were washed with brine (20 ml)
4. dry with materialdried over MgSO4
5. customThe solvent was removed under vacuum
6. customthe residual dark orange oil was chromatographed (ethyl acetate as eluent)