Dimethylformamide → HCID 58934821, compound

Temperature

110 °C

To the mixture of ethyl 6-methyl-2-(trifluoromethyl)-7-{[(trifluoromethyl) sulfonyl]-oxy}-2H-chromene-3-carboxylate (0.3 g, 0.7 mmol), potassium carbonate(0.378 g, 2.73 mmol), tetrakis(triphenylphosphine)palladium (0) (81 mg, 0.07 mmol) and 3 mL of anhydrous DMF was added trimethylboraxine(292 uL, 2.1 mmol). The resulting mixture was heated to 110° C., and stirred at 110° C. for two hrs. LC-MS indicated that the reaction was done. To the reaction was added 100 mL of EtOAc, the resulting organic solution was washed 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. It gave a white solid, about 180 mg. The purified white solid was dissolved in 3 mL of THF, to the resulting solution was added lithium hydroxide hydrate (118 mg, 2.8 mmol), 3 mL of water and 3 mL of ethanol, the resulting solution was heated to 80° C. and stirred for 45 min. After cooling to room temperature, the volatiles were removed on rotavapor, the residue was diluted with water, and acidified in ice bath with ice cold dilute hydrochloric acid. Plenty of white precipitates were formed. The solid was filtered and washed with water, and dried in vacuum. The crude product was then purified on reverse phase HPLC. It gave a white solid, 70 mg. 1H NMR (CDCl3/CD3OD/300 MHz) 7.73(s, 1H), 6.97(s, 1H), 6.79(s, 1H), 5.65(q, J=6.6 Hz), 2.25(s, 3H), 2.19(s, 3H). 13C NMR(CDCl3/ CD3OD/300 MHz) 167.0, 151.8, 143.2, 138.3, 131.0, 130.4, 123.9(q, J=287.9 Hz), 117.1, 116.9, 115.2, 70.7(q, J=32.7 Hz), 20.5, 18.9. 19F NMR(CDCl3/ CD3OD/300 MHz) −78.97(d, J=6.5 Hz). LC-MS (ES+):273.2 (M+1, 100). High resolution Mass (ES−): m/z calc. For C13H10F3O3: 271.0582(M−H), found: 271.0563.

1. additionwas added trimethylboraxine(292 uL, 2.1 mmol)
2. washthe resulting organic solution was washed with brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customAfter removing the volatiles
5. customthe residue was purified on silica gel column with 1:9 EtOAc/hexane
6. customIt gave a white solid, about 180 mg
7. temperaturethe resulting solution was heated to 80° C.
8. stirringstirred for 45 min
9. temperatureAfter cooling to room temperature
10. customthe volatiles were removed on rotavapor
11. additionthe residue was diluted with water
12. customPlenty of white precipitates
13. customwere formed
14. filtrationThe solid was filtered
15. washwashed with water
16. customdried in vacuum
17. customThe crude product was then purified on reverse phase HPLC
18. customIt gave a white solid, 70 mg

ORD record

ord-9d27519f8dc6426cb0c5d28189c575bc

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07259266B2