Sodium hydride → 3-Fluoro-alpha-(4-fluorophenyl)-benzenepropanoic acid

HRID 232538Notes

Reaction equation

HRID 232538 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([O:13]C)=[O:12])=[CH:6][CH:5]=1.[F:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH2:19]Br>O1CCCC1>[F:15][C:16]1[CH:17]=[C:18]([CH2:19][CH:10]([C:7]2[CH:8]=[CH:9][C:4]([F:3])=[CH:5][CH:6]=2)[C:11]([OH:13])=[O:12])[CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680073-Fluorobenzyl bromideHCID 2733233Methyl 2-(4-fluorophenyl)acetate

Product 1

HCID 233587593-Fluoro-alpha-(4-fluorophenyl)-benzenepropanoic acidYield 62.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 10.8 g of 60% sodium hydride in 400 mL of tetrahydrofuran was added 44.7 g of methyl 4-fluorophenylacetate dropwise. Then, 50 g of 3-fluorobenzyl bromide was added dropwise. The mixture was then heated to reflux for approximately 18 hours. After this time, the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ether and 5% aqueous sodium bicarbonate, and the ether extracts were dried over magnesium sulfate and concentrated to 77.57 g of a yellow oil. The crude product was combined with 275 mL of methanol, 20 mL of 50% aqueous NaOH and 50 mL of H2O and the mixture was refluxed for about 18 hours. The reaction was then cooled to room temperature, concentrated and partitioned between water and ether. The aqueous extracts were made acidic with concentrated HCl and extracted with ether. The ether extracts were dried over MgSO4, filtered, concentrated and the crude product was triturated with hexane to afford 43.62 g of a white solid; mp 92°-94° C.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureto reflux for approximately 18 hours
  3. filtrationfiltered
  4. customThe filtrate was partitioned between ether and 5% aqueous sodium bicarbonate
  5. dry with materialthe ether extracts were dried over magnesium sulfate
  6. concentrationconcentrated to 77.57 g of a yellow oil
  7. temperaturethe mixture was refluxed for about 18 hours
  8. temperatureThe reaction was then cooled to room temperature
  9. concentrationconcentrated
  10. custompartitioned between water and ether
  11. extractionextracted with ether
  12. dry with materialThe ether extracts were dried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customthe crude product was triturated with hexane

Sources & evidence

ORD record
ord-b3d68a963b9c41af98c259f6105d616c
Source dataset
uspto-grants-1997_01
Patent number
US05591729

Reaction notes

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