Ethyl Acetate → HCID 58934466, compound

HRID 855151Notes

Reaction equation

HRID 855151 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[O:8][CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([O:19]CC)=[O:18])=[CH:5]2.[C:22](=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1.C(OCC)(=O)C>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:22][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[O:8][CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([OH:19])=[O:18])=[CH:5]2

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 58934475HCID 58934475, compound

Product 1

HCID 58934466HCID 58934466, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To the mixture of ethyl 6-bromo-7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate (2.2g, 6 mmol), potassium carbonate(3.22g, 23.4mmol), and tetrakis(triphenylphosphine)palladium (0) (700 mg, 0.6 mmol) in 18 ml of anhydrous DMF was added trimethylboroxine(2.5 mL, 9 mmol). The resulting mixture was heated to 110° C. under nitrogen atmosphere for 15 hrs. After cooling to room temperature, to the reaction was added 200 mL of ethyl acetate, the resulting organic phase was washed with brine, and dried over anhydrous magnesium sulfate. After removing the solvents, the residue was purified on a short silica gel column with hexane/EtOAc mixture. The collected fraction was then evaporated to dryness. 300 mg of the purified intermediate was then dissolved in 9 mL of 1:1:1 THF/EtOH/Water, followed by addition of lithium hydroxide hydrate (102 mg). The resulting solution was heated to 80° C. for 1.5 hrs. The volatiles were then removed, the residue was diluted with water, and acidified at 0° C. with dilute hydrochloric acid. Plenty of precipitates were formed. The product was then extracted with ethyl acetate. After removing the solvents, the crude product was purified on reverse phase HPLC. Light yellow solid. 1H NMR (CDCl3/CD3OD/300 MHz) 7.76(s, 1H), 7.07(d, J=8.1 Hz, 1H), 6.68(d, J=9.9 Hz, 1H), 5.65(q, J=6.9 Hz, 1H), 2.20(s, 3H). 19F NMR(CDCl3/CD3OD/300 MHz) −78.93(d, J=6.9 Hz), −107.11(t, J=7.9 Hz). 13C NMR(CDCl3/CD3OD/300 MHz) 168.0, 165.8, 162.3, 153.2(d, J=12.8 Hz), 138.4, 132.2, 123.6(q, J=287.5 Hz), 119.8(d, J=18.5 Hz), 115.0(d, J=43.2 Hz), 104.1(d, J=27.1 hz), 70.7(q, J=33.3 Hz), 14.0(d, J=3.2 Hz). LC-MS(ES+): 277.2(M+1, 100). Hight resolution mass(ES−): m/z calc. For C12H8F4O3: 275.0337(M−H), found: 275.0341.

Workup

  1. temperatureAfter cooling to room temperature, to the reaction
  2. washthe resulting organic phase was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customAfter removing the solvents
  5. customthe residue was purified on a short silica gel column with hexane/EtOAc mixture
  6. customThe collected fraction was then evaporated to dryness
  7. dissolution300 mg of the purified intermediate was then dissolved in 9 mL of 1:1:1 THF/EtOH/Water
  8. additionfollowed by addition of lithium hydroxide hydrate (102 mg)
  9. temperatureThe resulting solution was heated to 80° C. for 1.5 hrs
  10. customThe volatiles were then removed
  11. additionthe residue was diluted with water
  12. customacidified at 0° C. with dilute hydrochloric acid
  13. customPlenty of precipitates
  14. customwere formed
  15. extractionThe product was then extracted with ethyl acetate
  16. customAfter removing the solvents
  17. customthe crude product was purified on reverse phase HPLC

Sources & evidence

ORD record
ord-ca3547a2e03c416dad9873b68313c3c1
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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