反应详情

温度

50 °C

To a stirred solution of 6.0 g of 1-(3-tert-butyl-5-(6-hydroxynaphthalen-2-yl)-4-methoxyphenyl)pyrimidine-2,4(1H,3H)-dione (14.4 mmol, 1.0 equivalent) in 60 mL of N,N-dimethylformamide was added 4.0 g of 325-mesh potassium carbonate (29 mmol, 2.0 equivalents). 1,1,1,2,3,3,3-heptafluoropropane-2-sulfonyl fluoride (3.6 g, 14.3 mmol, 1.0 equivalents) was added over 30 minutes, and the mixture was stirred for 2 hours. An additional portion of 1,1,1,2,3,3,3-heptafluoropropane-2-sulfonyl fluoride (0.21 g, 0.83 mmol, 0.06 equivalents) was added, and the mixture was stirred for 1.5 hours. The inorganic solids were separated by filtration, and the flask and filter cake were rinsed with 75 mL of ethyl acetate. The solution was diluted with an additional 75 mL of ethyl acetate and the resultant solution was washed four times with 50 mL portions of 10 wt % aqueous sodium chloride, followed by 50 mL of saturated aqueous sodium chloride solution. The organic solution was dried over sodium sulfate, the drying agent was filtered off and the organic solution was concentrated in vacuo. The resultant oil was dissolved in 7 mL of ethyl acetate, which resulted in crystallization after stirring for a few minutes. Heptanes (90 mL) were added slowly to the stirred mixture. The product was isolated by filtration, washed with 20 mL of heptanes and dried in vacuo with heating at 50° C. The title compound was isolated as a white solid (8.30 g, 89% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.05 (s, 1H), 7.95 (d, J=9.6 Hz, 1H), 7.93 (d, J=9.6 Hz, 1H), 7.83 (dd, J=8.5, 1.7 Hz, 1H), 7.78 (d, J=2.4 Hz, 1H), 7.40 (dd, J=8.9, 2.4 Hz, 1H), 7.36 (d, J=7.9 Hz, 1H), 7.27-7.23 (m, 2H), 5.81 (d, J=7.9 Hz, 1H), 3.29 (s, 3H), 1.46 (s, 9H) (NH not observed in this spectrum). 13C NMR (101 MHz, CDCl3) δ ppm 162.7 (C), 157.5 (C), 149.8 (C), 146.9 (C), 145.0 (C), 144.5 (CH), 137.2 (C), 135.1 (C), 133.0 (C), 132.2 (C), 132.2 (C), 130.5 (CH), 128.5 (CH), 128.1 (CH), 127.4 (CH), 127.2 (CH), 124.4 (CH), 119.9 (CH), 118.9 (CH), 102.4 (CH), 60.9 (CH3), 35.8 (C), 30.8 (CH3). 19F NMR (564 MHz, DMSO) δ ppm −71.08 (6F), −167.87 (1F). LC-MS m/z 649.1 [M+H]+.

1. stirringthe mixture was stirred for 1.5 hours
2. customThe inorganic solids were separated by filtration
3. filtrationthe flask and filter cake
4. washwere rinsed with 75 mL of ethyl acetate
5. additionThe solution was diluted with an additional 75 mL of ethyl acetate
6. washthe resultant solution was washed four times with 50 mL portions of 10 wt % aqueous sodium chloride
7. dry with materialThe organic solution was dried over sodium sulfate
8. filtrationthe drying agent was filtered off
9. concentrationthe organic solution was concentrated in vacuo
10. dissolutionThe resultant oil was dissolved in 7 mL of ethyl acetate
11. customwhich resulted in crystallization
12. stirringafter stirring for a few minutes
13. customThe product was isolated by filtration
14. washwashed with 20 mL of heptanes
15. customdried in vacuo