Ethanol → HCID 58934936, compound

HRID 855149Notes

Reaction equation

HRID 855149 reaction equation
C([C:3]1([C:18]([F:21])([F:20])[F:19])[C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([Cl:17])[C:9]=2[F:16])[O:4]1)C.O.[OH-].[Li+].C(O)C>C1COCC1.O>[Cl:17][C:8]1[C:9]([F:16])=[C:10]2[C:5](=[CH:6][CH:7]=1)[O:4][CH:3]([C:18]([F:21])([F:19])[F:20])[C:12]([C:13]([OH:15])=[O:14])=[CH:11]2

Participants

6

Reactant 3

HCID 702EthanolHCID 168937Lithium hydroxide, monohydrateHCID 69517261HCID 69517261, compound

Product 1

HCID 58934936HCID 58934936, compoundYield 29.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the solution of ethyl 6-chloro-5-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid (1.1 g, 3.4 mmol) in 5 mL of THF was added a solution of lithium hydroxide hydrate (0.72 g, 17 mmol) in 5 mL of water. To the resulting mixture was added 5 mL of ethanol. The resulting solution was heated to reflux over three hrs. The reaction turned red. After cooling to room temperature, the volatiles were removed, the residue was diluted with water. The resulting solution was acidified at 0° C. with ice cold dilute hydrochloric acid. The product was then extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate. After removing the solvent, the residue was purified on reverse phase HPLC. It gave a yellow solid (0.3 g). LC-MS(ES+) 297.2(M+1, 100). 1H NMR (CDCl3/CD3OD/400 MHz) 7.85(s, 1H), 7.24(m, 1H), 6.69(d, J=8.8 Hz, 1H), 5.63(q, J=6.4 Hz, 1H). 19F (CDCl3/CCD3OD/400 MHz) −78.94(d, J=6.8 Hz), −111.92(d, J=7.5 Hz). 13C NMR(CDCl3/CD3OD/400 MHz) 165.4, 155.0(d, J=64.4 Hz), 152.3, 133.2, 129.4, 123.3 (q, J=287.3 Hz) 118.5 114.2(d, J=4.3 Hz), 112.6, 110.1 (d, J=4.7 Hz), 70.9(q, J=33.2 Hz). HRSM((EI+) m/z calc. for (C11H5ClF4O3): 295.9863(M+), found 295.9875(M+).

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux over three hrs
  3. customthe volatiles were removed
  4. additionthe residue was diluted with water
  5. customwas acidified at 0° C. with ice cold dilute hydrochloric acid
  6. extractionThe product was then extracted with ethyl acetate
  7. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  8. customAfter removing the solvent
  9. customthe residue was purified on reverse phase HPLC

Sources & evidence

ORD record
ord-1dd1fb74503c462ab5e4f7ca966f08f8
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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