反应详情

A solution of 0.34 g (0.63 mmol) of Ethyl 6-chloro-7-(2-methyl-4-iodophenoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate and 68 mg (0.76 mmol) of copper (I) cyanide in 4 mL of anhydrous dimethylformamide was stirred to 130° C. overnight. LC-MS indicated that the reaction was completed. After cooling to room temperature, the reaction was dumped into 100 mL of ethyl acetate. The organic solution was then washed with 30% aqueous ethylenediamine solution three times to remove cupper, then washed with with brine, and dried over anhydrous magnesium sulfate. After removing the volatiles, the residue was purified on silica gel column with 1:9 EtOAc/hexane. The obtained compound (0.14 g, 0.32 mmol) was dissolved in 3 mL of tetrahydrofuran. To the resulting solution was added a solution of 67.2 mg (1.6 mmol) of lithium hydroxide (LiOH.2H2O) in 3 mL of water, followed by addition of 3 mL of ethanol. The resulting solution was heated to 50° C. for one hr, then at rt for one hr. The volatiles were removed. The residue was diluted with water, and acidified at 0° C. with dilute hydrochloric acid to pH=1, and the product was extracted with ethyl acetate. The combined organic extracts were washed with birne, and dried over anhydrous magnesium sulfate. After removing the volatiles, the residue was purified on reverse phase HPLC. The product was obtained as white solid, 70 mg, purity=100%, yield=27%. 1H NMR (CDCl3/CD3OD/300 MHz) 7.66(s, 1H), 7.56(d, 1H), 7.46(dd, J=1.5, 8.4 Hz, 1H), 7.34(s, 1H), 6.80(d, J=8.4 Hz, 1H), 6.51(s, 1H), 5.66(q, J=6.9 Hz, 1H), 2.31(s, 3H); MS (ES+) 410 (M+1, 100); HRMS (ES−) m/z calcd for (M−1; C19H10ClF3NO4) 408.0245, found 408.0227.

1. washThe organic solution was then washed with 30% aqueous ethylenediamine solution three times
2. customto remove cupper
3. washwashed with with brine
4. dry with materialdried over anhydrous magnesium sulfate
5. customAfter removing the volatiles
6. customthe residue was purified on silica gel column with 1:9 EtOAc/hexane
7. temperatureThe resulting solution was heated to 50° C. for one hr
8. customThe volatiles were removed
9. additionThe residue was diluted with water
10. customacidified at 0° C. with dilute hydrochloric acid to pH=1
11. extractionthe product was extracted with ethyl acetate
12. washThe combined organic extracts were washed with birne
13. dry with materialdried over anhydrous magnesium sulfate
14. customAfter removing the volatiles
15. customthe residue was purified on reverse phase HPLC
16. customThe product was obtained as white solid, 70 mg, purity=100%, yield=27%