反应详情

To a suspension of 4-(2-fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide (258 mg, 0.52 mmol) in methanol (10 mL) was added hydrochloric acid (1.0 mL, 1M solution, 1.0 mmol) and the reaction mixture stirred at room temperature for 1 hour. The reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was separated and washed with water then brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—SPE, gradient 0-100% ethyl acetate in cyclohexane) to give the title compound as a white solid (140 mg, 57%). LCMS (Method A): RT=9.72 min, [M+H]+=474. 1H NMR (CD3OD, 400 MHz) 8.57 (1H, s), 7.71 (1H, d, J=8.53 Hz), 7.69-7.61 (1H, m), 7.51 (1H, dd, J=10.43, 1.94 Hz), 7.33 (1H, d, J=8.54 Hz), 6.67 (1H, t, J=8.63 Hz), 3.92 (2H, t, J=4.60 Hz), 3.70 (2H, t, J=4.60 Hz).

1. concentrationThe reaction mixture was concentrated in vacuo
2. customthe residue partitioned between ethyl acetate and saturated aqueous NaHCO3
3. customThe organic layer was separated
4. washwashed with water
5. dry with materialbrine, dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo