Methyl iodide → 2-(3-Bromophenyl)-2-methylpropanoic acid

HRID 2110706Notes

Reaction equation

HRID 2110706 reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.[Br:9][C:10]1[CH:11]=[C:12]([CH:16]([CH3:20])[C:17]([OH:19])=[O:18])[CH:13]=[CH:14][CH:15]=1.CI>C1COCC1.CCCCCCC.C(C1C=CC=CC=1)C.C1COCC1>[Br:9][C:10]1[CH:11]=[C:12]([C:16]([CH3:2])([CH3:20])[C:17]([OH:19])=[O:18])[CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 127979542-(3-Bromophenyl)propanoic acid2×

Product 1

HCID 128051282-(3-Bromophenyl)-2-methylpropanoic acidYield 91%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Procedure

To a solution of LDA in THF/n-heptane/ethylbenzene (1.8 M, 17 mL) at 0° C. is added a solution of 2-(3-bromo-phenyl)-propionic acid [3 g, 13.9 mmol, Intermediate (69)] in THF (5 mL) dropwise during 15 minutes. Stir for 1 hour, followed by addition of methyl iodide (4.93 g, 34.8 mmol) in THF (5 mL) dropwise during 10 min. The reaction mixture is stirred for 15 hours, quenched with 2 N hydrochloric acid, concentrated in vacuo, and diluted with ether (150 mL). The ether layer is washed with 2 N hydrochloric acid, extracted three times with 2 N sodium hydroxide (50 mL), Combined sodium hydroxide layers are acidified with 6 N hydrochloric acid to pH=1 and extracted three times with ether (75 mL). Combined organic layers are washed with brine, dried over sodium sulfate and concentrated to obtain 2-(3-bromo-phenyl)-2-methyl-propionic acid as a solid (3.08 g, 91% yield), which is used without further purification. LC/MS: 243 (M+H)

Workup

  1. stirringThe reaction mixture is stirred for 15 hours
  2. customquenched with 2 N hydrochloric acid
  3. concentrationconcentrated in vacuo
  4. additiondiluted with ether (150 mL)
  5. washThe ether layer is washed with 2 N hydrochloric acid
  6. extractionextracted three times with 2 N sodium hydroxide (50 mL)
  7. extractionextracted three times with ether (75 mL)
  8. washCombined organic layers are washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-aa4390fcc0c0467eb1b11e8180aec6f1
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Reaction notes

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