Sodium hydride → Di-p-tolylhydroxyacetic acid methyl ester

HRID 650524Notes

Reaction equation

HRID 650524 reaction equation
[H-].[Na+].[C:3]1([CH3:21])[CH:8]=[CH:7][C:6]([CH:9]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[C:10]([O:12][CH3:13])=[O:11])=[CH:5][CH:4]=1.C1C=C(Cl)C=C(C(OO)=[O:30])C=1>O1CCCC1>[CH3:13][O:12][C:10](=[O:11])[C:9]([C:6]1[CH:7]=[CH:8][C:3]([CH3:21])=[CH:4][CH:5]=1)([C:14]1[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=1)[OH:30]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 70297m-Chloroperbenzoic acidHCID 6452857Benzeneacetic acid, 4-methyl-alpha-(4-methylphenyl)-, methyl ester

Product 1

HCID 22574226Di-p-tolylhydroxyacetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of NaH (255 mg, 10.6 mmol) in tetrahydrofuran (50 mL) was cooled to 0° C. and treated with a solution of 21 (2.29 g, 9.00 mmol) in tetrahydrofuran. The cooling bath was removed and DMF (1 mL) was added to the reaction. The resulting mixture was stirred at room temperature overnight. The mixture was treated with TMS-Cl (10 mL of 1M THF solution) and stirred at room temperature (2 h). The reaction was treated with solid MCPBA (85%, 3.49 g, 17.2 mmol) and stirred at room temperature overnight. The reaction was quenched with tetrabutylammonium fluoride and diluted with ethyl acetate and water. The aqueous layer was extracted with two additional portions of ethyl acetate and the combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. Flash chromatography on silica gel (dichloromethane/hexane) afforded the title compound (22).

Workup

  1. customThe cooling bath was removed
  2. additionDMF (1 mL) was added to the reaction
  3. additionThe mixture was treated with TMS-Cl (10 mL of 1M THF solution)
  4. stirringstirred at room temperature (2 h)
  5. stirringstirred at room temperature overnight
  6. customThe reaction was quenched with tetrabutylammonium fluoride
  7. additiondiluted with ethyl acetate and water
  8. extractionThe aqueous layer was extracted with two additional portions of ethyl acetate
  9. washthe combined organic extracts were washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1e59d8c673084cfaaca910d58184b57a
Source dataset
uspto-grants-2001_08
Patent number
US06274583B1

Reaction notes

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