Acetyl chloride → Methyl 5-acetyl-2,4-dihydroxybenzoate

HRID 241817Notes

Reaction equation

HRID 241817 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([O:10]C(=O)C)=[CH:6][C:5]=1[OH:14].OS(C(F)(F)F)(=O)=O.[C:24](Cl)(=[O:26])[CH3:25].CCOC(C)=O>O>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([C:24](=[O:26])[CH3:25])[C:7]([OH:10])=[CH:6][C:5]=1[OH:14]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8857Ethyl AcetateHCID 62406Trifluoromethanesulfonic acidHCID 579902174-Acetoxy-2-hydroxy-benzoic acid methyl ester

Product 1

HCID 12482079Methyl 5-acetyl-2,4-dihydroxybenzoate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The toluene solution from Step 1 was cooled in an ice bath under N2 and triflic acid (9.44 L) added slowly over 3 h. On stirring a fine white solid was formed which dissolved on warming to RT over 20 h and then stirring at RT for 37 h to give a yellow solution. To the solution was added acetyl chloride (726 mL) and the solution stirred at RT for a further 1 h. This solution was cannulated into a stirred cooled (0° C.) solution of EtOAc (217.8 L) and NaOAc.3H2O (14.52 Kg) dissolved in water (145 L). The organic phase was washed with saturated brine (twice, 72.6 L), and was evaporated to 5.5 Kg. Toluene:Isopropanol (2:3) was added and the crystalline solid removed by filtration and dried to give 12.6 Kg (61% over 2 steps), mp 124-126° C.

Workup

  1. customwas formed which
  2. dissolutiondissolved
  3. stirringstirring at RT for 37 h
  4. customto give a yellow solution
  5. stirringthe solution stirred at RT for a further 1 h
  6. washThe organic phase was washed with saturated brine (twice, 72.6 L), and
  7. customwas evaporated to 5.5 Kg
  8. additionToluene:Isopropanol (2:3) was added
  9. customthe crystalline solid removed by filtration
  10. customdried
  11. customto give 12.6 Kg (61% over 2 steps), mp 124-126° C.

Sources & evidence

ORD record
ord-7010f9421ed44340b62180e8885bbc4e
Source dataset
uspto-grants-2014_02
Patent number
US08653084B2

Reaction notes

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