Methyl iodide → 2-Methyl-2-phenylpropane-1,3-diol

HRID 349713Notes

Reaction equation

HRID 349713 reaction equation
[C:1]1([C:7]([C:18]2C=CC=CC=2)([C:13](OCC)=[O:14])[C:8](OCC)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.IC.[H-].[Na+].C([O-])(O)=O.[Na+].[Li].[H-]>C1COCC1>[CH3:18][C:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)([CH2:13][OH:14])[CH2:8][OH:9]

Participants

8

Reactant 6

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 166653HydrideHCID 231689HCID 231689, compoundHCID 516892Sodium BicarbonateHCID 3028194Lithium

Product 1

HCID 906032-Methyl-2-phenylpropane-1,3-diol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl diphenylmalonate (10 g, 42.4 mmol) and iodomethane (6.6 g, 46.6 mmol) was mixed in anhydrous THF (200 ml) at room temperature before NaH powder was added in several portions. The reaction finished instantly with release of heat. After cooled down to room temperature, aqueous NaHCO3 solution was added to quench the reaction. The mixture was extracted with ethyl acetate, washed with water, brine, dried with Na2SO4 and concentrated. A clean NMR spectrum of the crude product identified it as the desired product. 1H NMR (500 MHz, CDCl3) δ ppm 1.26 (t, J=7.17 Hz, 6 H) 4.24 (m, 3 H) 7.34 (m, 5 H). The crude product was then dissolved in anhydrous THF (200 ml) and cooled to −20° C. Lithium aluminun hydride (42.4 mmol) was added via dropping funnel within 10 minutes. The reaction mixture was warmed up naturally to room temperature and quenched with ethyl acetate and water. The orgamic layer was washed with brine and dried with Na2SO4 before being concentated in-vacuo. The crude product was purified by silica flash chromatography using 50% ethyl acetate in hexanes to yield 4.35 grams (62% in two steps) of the desired product. 1H NMR (500 MHz, CDCl3) δ: 3.85 (m, 3 H) 3.98 (d, J=10.99 Hz, 2 H) 7.27 (m, 1 H) 7.38 (t, J=7.93 Hz, 2 H) 7.44 (m, 2 H).

Workup

  1. additionwas added in several portions
  2. temperatureof heat
  3. customto quench
  4. customthe reaction
  5. extractionThe mixture was extracted with ethyl acetate
  6. washwashed with water, brine
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated
  9. dissolutionThe crude product was then dissolved in anhydrous THF (200 ml)
  10. temperaturecooled to −20° C
  11. customwithin 10 minutes
  12. temperatureThe reaction mixture was warmed up naturally to room temperature
  13. customquenched with ethyl acetate and water
  14. washThe orgamic layer was washed with brine
  15. dry with materialdried with Na2SO4
  16. customThe crude product was purified by silica flash chromatography

Sources & evidence

ORD record
ord-710ddad5567a4165b5df11c183ffd3e6
Source dataset
uspto-grants-2007_02
Patent number
US07179926B2

Reaction notes

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