反应详情

DMF (1 mL) was cooled to 0° C. and POCl3 (0.25 mL) was added and stirred for 10 min Compound 203 (336 mg, 1.69 mmol) in DMF (2 mL) was added drop-wise over 10 min. The solution was stirred for an additional 1 h warming to rt then heated to 85° C. and allowed to react for an additional 4 h. The solution was poured into ice-cold 1 N NaOH (40 mL) and stirred for 30 minutes in an ice-bath resulting in the formation of a precipitate. The precipitate was collected, washed with cold H2O and dried overnight at 40° C. in a vacuum desiccator to yield a cream-colored solid. The sample was further purified by chromatography (7% to 20% EtOAc/hexanes) to obtain a white solid (178 mg, 43%): mp 236-239° C. TLC Rf 0.51 (30% EtOAc/hexanes). 1H NMR (600 MHz, d4-MeOH) δ 10.22 (s, 1H), 7.79 (d, 1H, J=2.46 Hz), 7.45-7.43 (d, 1H, J=9 Hz), 7.06-7.04 (dd, 1H, J1=8.94 Hz, J2=2.52 Hz), 3.86 (s, 3H). 13C NMR (150 MHz, d4-MeOH) δ 186.2, 159.0, 132.0, 127.1, 123.4, 121.6, 118.2, 117.2, 114.8, 104.1, 56.2. 19F NMR (376 MHz, CDCl3) δ −58.7 (s, 3F). Elemental analysis calculated for C11H8F3NO2: C, 54.33; H, 3.32; N, 5.76. Found: C, 54.53; H, 3.32; N, 5.76.

1. additionwas added drop-wise over 10 min
2. temperaturethen heated to 85° C.
3. customto react for an additional 4 h
4. stirringstirred for 30 minutes in an ice-bath
5. customresulting in the formation of a precipitate
6. customThe precipitate was collected
7. washwashed with cold H2O
8. customdried overnight at 40° C. in a vacuum desiccator
9. customto yield a cream-colored solid
10. customThe sample was further purified by chromatography (7% to 20% EtOAc/hexanes)