Benzoyl chloride → Methyl 3-hydroxy-5-[(phenylcarbonyl)oxy]benzoate

HRID 418016Notes

Reaction equation

HRID 418016 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[C:6]([OH:11])[CH:5]=1.C(=O)([O-])[O-].[K+].[K+].[C:19](Cl)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(OC(C)C)(=O)C>O.CN(C)C=O>[OH:11][C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([O:10][C:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:26])[CH:7]=1)[C:3]([O:2][CH3:1])=[O:12]

Participants

7

Reactant 4

HCID 7412Benzoyl chloride2×HCID 7915Isopropyl AcetateHCID 11430Potassium CarbonateHCID 75076Methyl 3,5-Dihydroxybenzoate

Product 1

HCID 59447453Methyl 3-hydroxy-5-[(phenylcarbonyl)oxy]benzoateYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
47 °C

Procedure

To a flask fitted with thermometer, condenser, overhead stirrer, pH probe and nitrogen line was added methyl-3,5-dihydroxybenzoate (1.0 eq), 325 mesh potassium carbonate (3.0 eq) and dimethylformamide (DMF) (4 vols) under a nitrogen atmosphere. The mixture was heated to 47° C. for 1 hour, then benzoyl chloride (1.0 eq) was added slowly drop-wise via syringe pump over approximately 2 hours. Further benzoyl chloride was added (0.1 eq) over 20 minutes via syringe pump. The reaction mixture was held for 1.5 hours, then water (10 vols) and iso-propyl acetate (6 vols) were added. The reaction mixture was agitated for 30 minutes and then the layers were separated. The aqueous layer was re-extracted with a further charge of iso-propyl acetate (6 vols). The batch was separated, and the combined organic layers were washed with saturated brine (6 vols), then with a solution of 0.1N hydrochloric acid/brine. The iso-propyl acetate was distilled to dryness on the rotary evaporator. Iso-propyl acetate (6 vols) was added, and distilled to dryness on the rotary evaporator. Toluene (6 vols) was added and distilled to dryness on the rotary evaporator. Toluene (3.5 vols) was added and the reaction slurried for 30 minutes. The solid was filtered off and dried at 20° C.-40° C. to give the desired product as a solid (corrected yield 72%).

Workup

  1. customTo a flask fitted with thermometer, condenser, overhead stirrer, pH probe and nitrogen line
  2. customthe layers were separated
  3. extractionThe aqueous layer was re-extracted with
  4. additiona further charge of iso-propyl acetate (6 vols)
  5. customThe batch was separated
  6. washthe combined organic layers were washed with saturated brine (6 vols)
  7. distillationThe iso-propyl acetate was distilled to dryness on the rotary evaporator
  8. additionIso-propyl acetate (6 vols) was added
  9. distillationdistilled to dryness on the rotary evaporator
  10. additionToluene (6 vols) was added
  11. distillationdistilled to dryness on the rotary evaporator
  12. additionToluene (3.5 vols) was added
  13. waitthe reaction slurried for 30 minutes
  14. filtrationThe solid was filtered off
  15. customdried at 20° C.-40° C.

Sources & evidence

ORD record
ord-79323d8e8fe3419f88b27f07d8a6b8f2
Source dataset
uspto-grants-2012_01
Patent number
US08093252B2

Reaction notes

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