反应详情

温度

110 °C

To the mixture of ethyl 6-chloro-5-iodo-2-(trifluoromethyl)-2H-chromene-3-carboxylate (0.3g, 0.7 mmol), potassium carbonate(109 mg, 2.87 mmol) and tetrakistriphenyl-palladium (0) (81 mg, 0.07 mmol) in 3 mL of anhydrous DMF was added triethylboron (1.0M/THF, 1.05 mL, 1.05 mmol) under nitrogen. The resulting mixture was heated to 110° C. for five hrs. The reaction was cooled to room temperature, and diluted with 100 mL of ethyl acetate. The resulting organic phase was washed with brine. After removing the solvent, the residue was dissolved in 3 mL of THF, followed by addition of a solution of lithium hydroxide hydrate in 3 mL of water. To the resulting mixture was further added 3 mL of ethanol. The resulting solution was then heated to 80° C. for three hrs. The volatiles were then removed. The residue was diluted with water, and acidified in an ice/water bath with dilute hydrochloric acid. The product was extracted with ethyl acetate. The organic extracts were washed with brine, and dried over anhydrous magnesium sulfate. After removing the solvent, the residue was purified on short silica gel with 3:7 EtOAc/hexane+1% HOAc to remove the polar impurities. After concentrating the collected fraction, the residue was further purified on reverse phase HPLC. It gave 75 mg slightly yellow solid. M.P.=171.5-172.5° C. 1H NMR (CDCl3/400 Mz), 8.07(s, 1H), 7.32(d, J=8.8 Hz, 1H), 6.82(d, J=8.8 Hz, 1H), 5.65(q, J=6.8 Hz, 1H), 2.91(m, 2H), 1.18(t, J=7.6 Hz, 3H). 13C NMR(CDCl3/400 MHz) 169.5, 152.8, 141.5, 136.5, 134.1, 127.7, 123.4(q, J=287.7 Hz), 118.6, 116.3, 115.5, 69.8(q, J=33.4 Hz), 23.1, 14.7. 19F NMR(CDCl3/400 Mz) −78.72(d, J=6.8 Hz). MS(ES−)=305.0 (M−H, 100). High resolution MS(ES−), m/e calc. For C13H10ClF3O3: 305.0198 (M−H), found: 305.0157.

1. temperatureThe reaction was cooled to room temperature
2. washThe resulting organic phase was washed with brine
3. customAfter removing the solvent
4. dissolutionthe residue was dissolved in 3 mL of THF
5. additionfollowed by addition of a solution of lithium hydroxide hydrate in 3 mL of water
6. temperatureThe resulting solution was then heated to 80° C. for three hrs
7. customThe volatiles were then removed
8. additionThe residue was diluted with water
9. customacidified in an ice/water bath with dilute hydrochloric acid
10. extractionThe product was extracted with ethyl acetate
11. washThe organic extracts were washed with brine
12. dry with materialdried over anhydrous magnesium sulfate
13. customAfter removing the solvent
14. customthe residue was purified on short silica gel with 3:7 EtOAc/hexane+1% HOAc
15. customto remove the polar impurities
16. concentrationAfter concentrating the collected fraction
17. customthe residue was further purified on reverse phase HPLC
18. customIt gave 75 mg slightly yellow solid