Hydrochloric Acid → Methyl (4-Hydroxybenzoyl)acetate

HRID 369694Notes

Reaction equation

HRID 369694 reaction equation
[CH3:1][C:2]([C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1)=[O:3].[H-].[Na+].[C:13](=O)([O:16]C)[O:14][CH3:15].Cl>CN(C=O)C>[OH:10][C:7]1[CH:8]=[CH:9][C:4]([C:2]([CH2:1][C:13]([O:14][CH3:15])=[O:16])=[O:3])=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 74694'-HydroxyacetophenoneHCID 12021Dimethyl CarbonateHCID 24758Sodium hydride

Product 1

HCID 508465Methyl (4-Hydroxybenzoyl)acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 4-hydroxyacetophenone (500 g) in DMF (1.5 L) was slowly added to a suspension of sodium hydride (331 g) in DMF. The mixture was stirred for 15 min. till gas evolution had subsided. Dimethyl carbonate (1.55 L) was added and the reaction stirred overnight at room temperature. The reaction was worked up by pouring into ice (15 LB) followed by acidification to pH 2 with hydrochloric acid. The aqueous mixture was extracted with ethyl acetate (3×5 L) and this was washed with water (3×1 L) and brine, then dried (Na2SO4), filtered, and concentrated. The crude product was purified by chromatography on silica gel (10 Kg) with 15 to 40% ethyl acetate-hexane. The chromatographed product was recrystallized twice from ethyl acetate-hexane to yield 313 gm first crop material as a white powder with mp 90-92° C.

Workup

  1. stirringthe reaction stirred overnight at room temperature
  2. additionby pouring into ice (15 LB)
  3. extractionThe aqueous mixture was extracted with ethyl acetate (3×5 L)
  4. washthis was washed with water (3×1 L) and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by chromatography on silica gel (10 Kg) with 15 to 40% ethyl acetate-hexane
  9. customThe chromatographed product was recrystallized twice from ethyl acetate-hexane

Sources & evidence

ORD record
ord-84050c36047e40ef812d630528e50249
Source dataset
uspto-grants-2000_10
Patent number
US06140310

Reaction notes

Loading…