Benzyl Bromide → Methyl 2-(2-methoxyphenyl)-3-phenylpropanoate

HRID 1714514Notes

Reaction equation

HRID 1714514 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11].C1COCC1.C([N-]C(C)C)(C)C.[Li+].[CH2:27](Br)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CCCCCCC.C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:10]([O:12][CH3:13])=[O:11]

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 8028TetrahydrofuranHCID 99590Methyl 2-methoxybenzeneacetateHCID 2724682Lithium diisopropylamide

Product 1

HCID 66695010Methyl 2-(2-methoxyphenyl)-3-phenylpropanoateYield 35%

Reagents, catalysts & solvents 1

HCID 21263495Tetrahydrofuran heptaneSolvent

Conditions

Temperature
0 °C

Procedure

A 500 mL round-bottom flask is charged with methyl 2-(2-methoxyphenyl)acetate (8.496 g, 47 mmol, 1 eq) and THF (200 mL). The homogeneous mixture is cooled to 0° C. in an ice bath. Lithium diisopropyl amide (23.5 mL of a 2.0 M solution in heptane/THF) is added, maintaining a temperature less than 3° C. The reaction is stirred 45 minutes at this reduced temperature. Benzyl bromide (5.6 mL, 47 mmol, 1 eq) is added dropwise. The reaction is allowed to gradually warm to room temperature and is stirred for 18 hours. The reaction is quenched with 1N HCl and extracted 3 times with equal portions of EtOAc. The combined extracts are washed with H2O and brine, dried over Na2SO4, filtered, and concentrated. The residue is purified over silica to afford 4.433 g (35%) of the desired compound. ESI+ MS 293 (M+Na).

Workup

  1. temperaturemaintaining a temperature less than 3° C
  2. temperatureto gradually warm to room temperature
  3. stirringis stirred for 18 hours
  4. customThe reaction is quenched with 1N HCl
  5. extractionextracted 3 times with equal portions of EtOAc
  6. washThe combined extracts are washed with H2O and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue is purified over silica

Sources & evidence

ORD record
ord-efb8167c13a648918ec6b4d5ab59c5c4
Source dataset
uspto-grants-2010_09
Patent number
US07795444B2

Reaction notes

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