Tetrahydrofuran → 3-Cyclopropyl-4-fluorobenzoic acid

HRID 401792Notes

Reaction equation

HRID 401792 reaction equation
[F:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][C:3]=1[CH:13]=[CH2:14].O.[OH-].[Li+].[CH2:18]1COCC1>O>[CH:13]1([C:3]2[CH:4]=[C:5]([CH:11]=[CH:12][C:2]=2[F:1])[C:6]([OH:8])=[O:7])[CH2:14][CH2:18]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 46941363Ethyl 4-fluoro-3-vinylbenzoate

Product 1

HCID 401517963-Cyclopropyl-4-fluorobenzoic acidYield 81%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of compound 3 ethyl 4-fluoro-3-vinylbenzoate (Preparation 54, 87 g, 0.42 mol, 1 eq) in THF (470 mL) and water (400 mL) was added lithium hydroxide monohydrate (35.1 g, 0.84 mol, 2.0 eq). The resulting mixture was stirred at 40° C. overnight. THF was removed in vacuum, then 6N hydrogen chloride solution was added dropwise until pH=2. The mixture was extracted with ethyl acetate (3×600 mL). The organic phase was dried over sodium sulfate and concentrated in vacuo to give title compound as a white solid (60.8 g, 0.34 mol, 81%).

Workup

  1. customTHF was removed in vacuum
  2. addition6N hydrogen chloride solution was added dropwise until pH=2
  3. extractionThe mixture was extracted with ethyl acetate (3×600 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5343e03f3aa84d798e9b05b541dea1d6
Source dataset
uspto-grants-2014_06
Patent number
US08741934B2

Reaction notes

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