Diethyl Carbonate → 6-Fluoro-4-hydroxycoumarin

HRID 2190919Notes

Reaction equation

HRID 2190919 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[CH2:12]([O:14]C(=O)OCC)C.CC(C)([O-])C.[K+]>O1CCCC1>[F:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:11][C:12](=[O:14])[CH:9]=[C:8]2[OH:10]

Participants

5

Reactant 3

HCID 7766Diethyl CarbonateHCID 959922-Acetyl-4-fluorophenolHCID 23665647Potassium tert-butoxide

Product 1

HCID 546914066-Fluoro-4-hydroxycoumarinYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-(5-Fluoro-2-hydroxy-phenyl)-ethanone (1.54 g, 10 mmol) and diethylcarbonate (2.42 mL, 20 mmol) were placed in a dry flask and dissolved in anhydrous tetrahydrofuran (30 mL.) The solution was then added drop-wise via cannula to a rapidly stirring solution of potassium tert-butoxide in tetrahydrofuran (1.0 M, 30 mL) The reaction was permitted to stir overnight (10 h) at room temperature under positive pressure of nitrogen. The crude reaction was concentrated under reduced pressure and partitioned between methyl tert-butyl ether and water. The layers were separated and the organic phase discarded. The aqueous phase was acidified to pH 5 and extracted three times with equal volumes of methylene chloride. The combined organic phases were dried over sodium sulfate and concentrated to give the title compound (1.4 g, 78% yield.) MS ESI(−) m/e: 179.16 (M−1).

Workup

  1. customThe crude reaction
  2. concentrationwas concentrated under reduced pressure
  3. custompartitioned between methyl tert-butyl ether and water
  4. customThe layers were separated
  5. extractionextracted three times with equal volumes of methylene chloride
  6. dry with materialThe combined organic phases were dried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f0fb5395ed3e4826ba67a0b53292924e
Source dataset
uspto-grants-2012_12
Patent number
US08324405B2

Reaction notes

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