Reaktion #942315

Reaktionsgleichung

lithium hydroxide hydrate

ethyl 7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

potassium carbonate

4-propylphenol

→

7-(4-Propylphenoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

Lösungsmittel

ethanol

water

EtOAc

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   WaschenThe resulting organic phase was washed with brine
2. 2
   Sonstigethe volatiles were removed
3. 3
   workup.ADDITIONTo the residue was added 3 mL of THF
4. 4
   TemperaturThe resulting solution was heated at 80° C. for 5 hrs
5. 5
   SonstigeThe volatiles were removed
6. 6
   workup.ADDITIONthe residue was diluted with water
7. 7
   Sonstigeacidified at 0° C. with dilute HCl to pH=1.0
8. 8
   Extraktionthe product was extracted with ethyl acetate
9. 9
   Trocknendried over anhydrous magnesium sulfate
10. 10
    SonstigeAfter removing the volatiles, it
11. 11
    Sonstigegave a light yellow oil
12. 12
    SonstigeThe residue was purified on reverse phase HPLC
13. 13
    SonstigeThe product was obtained as a light yellow solid, 80 mg (21%)

Vorschrift

To the mixture of ethyl 7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate (0.29 g, 1.0 mmol) and potassium carbonate (0.21g, 1.4 mmol) was added 4-propylphenol (0.153 mL, 1.1 mmol) and 3 mL of dry DMF. The resulting mixture was heated at 110° C. for 15 hrs. LC-MS indicated that the reaction was done. To the reaction was added 15 mL of EtOAc. The resulting organic phase was washed with brine, and the volatiles were removed. To the residue was added 3 mL of THF, and a solution of lithium hydroxide hydrate (105 mg, 2.5 mmol) in 3 mL of water. Then to the resulting mixture was added 3 mL of ethanol. The resulting solution was heated at 80° C. for 5 hrs. LC-MS indicated that the reaction was completed. The volatiles were removed, the residue was diluted with water, and acidified at 0° C. with dilute HCl to pH=1.0, the product was extracted with ethyl acetate, and dried over anhydrous magnesium sulfate. After removing the volatiles, it gave a light yellow oil. The residue was purified on reverse phase HPLC. The product was obtained as a light yellow solid, 80 mg (21%). M.P.=143.5-146.5° C. 1H(CDCl3/300 Mhz) 7.80(s, 1H), 7.18-7.13(m, 3H), 6.96(d, J=8.4 Hz, 2H), 6.59-6.52(m, 2H), 5.62(q, 1H, J=6.9 Hz), 2.57(t, 2H, J=6.9 Hz,), 1.67-1.57(m, 2H), 0.93(t, J=7.2 Hz, 3H). 13C NMR(CDCl3/300 MHz)169.5, 163.6, 155.5, 153.0, 139.7(d, J=13.0 Hz), 131.4, 130.2(d, J=5.3 Hz), 123.7(q, J=287.6 Hz), 120.6, 119.8, 113.7, 112.8, 112.0, 105.0, 70.7(q, J=33.5 Hz), 73.6, 24.9, 14.1. 19F(CDCl3/300 MHz) −78.96(d, J=6.9 Hz). LC-MS(EI+) 379.1 (M+1, 100). HRMS (EI+) m/z calcd for (C20H17F3O4) 378.1079(M+), found 378.1061.

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