Chloride → 4-(p-Fluorophenyl)butyric acid

HRID 2304921Notes

Reaction equation

HRID 2304921 reaction equation
Cl[Si](C)(C)C.[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=O)[CH2:14][CH2:15][C:16]([OH:18])=[O:17])=[CH:9][CH:8]=1.C(N(CC)CC)C.C([SiH](CC)CC)C.[Cl-].C(Cl)Cl>C1COCC1>[F:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17])=[CH:11][CH:12]=1

Participants

8

Reactant 6

HCID 312ChlorideHCID 6344DichloromethaneHCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 12052TriethylsilaneHCID 1013593-(4-Fluorobenzoyl)propionic acid

Product 1

HCID 685244-(p-Fluorophenyl)butyric acidYield 53.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., chlorotrimethylsilane (10.6 ml, 84.1 mmol) was added dropwise to a solution of 4-(4-fluorophenyl)-4-oxobutanoic acid (15.0 g, 76.5 mmol) and triethylamine (11.7 ml, 84.1 mmol) in THF (200 ml). The reaction mixture was stirred for 20 min at 0° C. The solid was filtered off. The solvent was removed from the solution. The residue was dissolved in DCM (200 ml). Triethylsilane (40 ml, 252 mmol) was added. An 1 N solution of titan(IV) chloride in DCM (229 ml, 229 mmol) was added dropwise while cooling with a water bath. The reaction mixture was stirred for 16 hours at room temperature. It was given onto ice water (300 ml). The phases were separated. The aqueous phase was extracted with DCM (100 ml). The combined organic phases were extracted with a saturated aqueous solution of sodium hydrogen carbonate (3×150 ml). The sodium hydrogen carbonate phases were combined and acidified with 1 N hydrochloric acid to pH 2. They were extracted with ethyl acetate (5×150 ml). The combined ethyl acetate layers were dried. The solvent was removed in vacuo to give 7.4 g of crude 4-(4-fluorophenyl)butyric acid, which was used in the next step without further purification.

Workup

  1. filtrationThe solid was filtered off
  2. customThe solvent was removed from the solution
  3. dissolutionThe residue was dissolved in DCM (200 ml)
  4. temperaturewhile cooling with a water bath
  5. stirringThe reaction mixture was stirred for 16 hours at room temperature
  6. customThe phases were separated
  7. extractionThe aqueous phase was extracted with DCM (100 ml)
  8. extractionThe combined organic phases were extracted with a saturated aqueous solution of sodium hydrogen carbonate (3×150 ml)
  9. extractionThey were extracted with ethyl acetate (5×150 ml)
  10. dry with materialThe combined ethyl acetate layers were dried
  11. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-d147500d377846f7a19ca7906df6b0e7
Source dataset
uspto-grants-2002_08
Patent number
US06437147B1

Reaction notes

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