4-Methoxyphenylacetic Acid → 1-(2-Chloro-4-fluorophenyl)-2-(4-methoxyphenyl)ethanone

HRID 1958685Notes

Reaction equation

HRID 1958685 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:20]([OH:22])=O)=[CH:15][CH:14]=1.[Cl:23][C:24]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:25]=1C(OC)=O>C1COCC1>[Cl:23][C:24]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:25]=1[C:20](=[O:22])[CH2:19][C:16]1[CH:15]=[CH:14][C:13]([O:12][CH3:11])=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 76904-Methoxyphenylacetic AcidHCID 2724254Sodium bis(trimethylsilyl)amideHCID 2763551Methyl 2-Chloro-4-fluorobenzoate

Product 1

HCID 610550851-(2-Chloro-4-fluorophenyl)-2-(4-methoxyphenyl)ethanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-60 °C

Procedure

230 ml of a 2M solution of NaHMDS in THF are introduced into 250 ml of THF under nitrogen. The solution is cooled to −60° C. and then 30.5 g of (4-methoxyphenyl)acetic acid in 120 ml of THF are added at this temperature. After 1 h 30 min at −60° C., 33 g of methyl 2-chloro-4-fluorobenzoate are added and the mixture is stirred at −60° C. for 45 min and then allowed to return to 0° C. The reaction medium is poured onto 500 ml of ice-cold 2N HCl and extracted with ether and the extract is washed with water and then with a saturated aqueous sodium chloride solution. After drying, concentrating to dryness and then crystallizing from pentane, 27.4 g of the expected compound are obtained.

Workup

  1. customto return to 0° C
  2. extractionextracted with ether
  3. washthe extract is washed with water
  4. customAfter drying
  5. concentrationconcentrating to dryness
  6. customcrystallizing from pentane, 27.4 g of the expected compound
  7. customare obtained

Sources & evidence

ORD record
ord-2e174b6ee3a54e178590c3224657349f
Source dataset
uspto-grants-2013_04
Patent number
US08410137B2

Reaction notes

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