反应详情

温度

70 °C

A stirred solution of 3,3-difluoro-2,2-dimethylpropanoic acid (26.6 mg, 0.193 mmol) in toluene (2 mL) at RT was added TEA (0.040 mL, 0.289 mmol) and DPPA (0.044 mL, 0.193 mmol) and the solution was stirred at 70° C. for 2 h. The reaction mass was cooled to RT and to it was added Intermediate 199B (30 mg, 0.096 mmol) dissolved in THF (1 mL) and the reaction mixture was stirred at RT for 12 h. The reaction mass was diluted with ethyl acetate (5 mL), the organic layer was separated, washed with 10% aqueous solution of NaHCO3, water, brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude compound was purified by preparative HPLC to afford Compound 199 as pale yellow solid (33 mg, 76% yield). The HPLC retention times are 2.173 min and 2.179 min (Methods J and K respectively); MS(ES): m/z=446.0 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.92 (s, 1H), 7.68 (s, 2H), 7.2-7.4 (m, 2H), 6.70 (s, 1H) 6.24-6.61 (m, 1H) 4.74 (s, 2H) 4.08-4.20 (m, 2H) 3.81-3.89 (m, 2H) 1.31 (s, 6H).

1. temperatureThe reaction mass was cooled to RT and to it
2. stirringthe reaction mixture was stirred at RT for 12 h
3. customthe organic layer was separated
4. washwashed with 10% aqueous solution of NaHCO3, water, brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationthe filtrate concentrated
8. customThe crude compound was purified by preparative HPLC