Methyl iodide → Methyl alpha-methylbenzeneacetate

HRID 867800Notes

Reaction equation

HRID 867800 reaction equation
C([Li])CCC.[CH3:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].C(NC(C)C)(C)C.[C:19]1([CH2:25][C:26]([O:28][CH3:29])=[O:27])C=CC=CC=1.CN(P(N(C)C)(N(C)C)=O)C.CI>C1COCC1.[Cl-].[NH4+].O>[C:8]1([CH:25]([CH3:19])[C:26]([O:28][CH3:29])=[O:27])[CH:7]=[CH:6][CH:11]=[CH:10][CH:9]=1

Participants

10

Reactant 6

HCID 6328Methyl iodideHCID 7559Methyl phenylacetateHCID 7912DiisopropylamineHCID 8058HexaneHCID 12679HexamethylphosphoramideHCID 178418339Butyllithium

Product 1

HCID 569653Methyl alpha-methylbenzeneacetateYield 86.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of n-butyl lithium in hexane (1.44N, 75 ml, 108 mmol) was added to a solution of diisopropylamine (11.3 g, 112 mmol) in anhydrous THF (200 ml) cooled at -20° C. under argon atmosphere, and the mixture was stirred for 30 minutes. The reaction mixture was cooled to -78° C. To this solution were added a solution of methyl phenylacetate (12.0 g, 80.0 mmol) in 15 ml of anhydrous THF and HMPA (20.6 g, 115 mmol). The mixture was stirred at -78° C. for 1 hour and then at -30° C. for 30 minutes. To this reaction solution was added a solution of methyl iodide (17.0 g, 120 mmol) in anhydrous THF (30 ml) at -78° C., and the mixture was stirred at -78° C. for 1.5 hours. The reaction mixture was allowed to warm to room temperature and diluted with an aqueous saturated solution of ammonium chloride (300 ml) and water (150 ml). The mixture was extracted with ether (400 ml). The aqueous layer was further extracted with ether (200 ml×2). The combined organic layers were washed with water (200 ml) and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was distilled (b.p. 92°-93° C./10 mmHg) to give an oil of methyl 2-phenylpropionate (11.3 g, 68.9 mmol, 86.1%). This compound was assigned to the structure by the following data:

Workup

  1. temperatureThe reaction mixture was cooled to -78° C
  2. stirringThe mixture was stirred at -78° C. for 1 hour
  3. waitat -30° C. for 30 minutes
  4. stirringthe mixture was stirred at -78° C. for 1.5 hours
  5. temperatureto warm to room temperature
  6. extractionThe mixture was extracted with ether (400 ml)
  7. extractionThe aqueous layer was further extracted with ether (200 ml×2)
  8. washThe combined organic layers were washed with water (200 ml) and brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated
  11. distillationThe residue was distilled (b.p. 92°-93° C./10 mmHg)

Sources & evidence

ORD record
ord-fa50535945384c00a38223ee93c036f9
Source dataset
uspto-grants-1988_10
Patent number
US04775692

Reaction notes

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