Ethyl Acetate → 7-Benzyloxy-6-methoxy-4-(3,4,5-trimethoxyphenyl)isocoumarin-3-carboxylic acid

HRID 1019409Notes

Reaction equation

HRID 1019409 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([O:32][CH3:33])=[CH:11][C:12]([C:18](=O)[C:19]2[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=2)=[C:13]([CH:17]=1)[C:14]([OH:16])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH:41](C(OC(C)(C)C)=O)[C:42]([O:44]C(C)(C)C)=[O:43].C(OCC)(=O)C>CN(C)C=O.O>[CH2:1]([O:8][C:9]1[CH:17]=[C:13]2[C:12]([C:18]([C:19]3[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=3)=[C:41]([C:42]([OH:44])=[O:43])[O:16][C:14]2=[O:15])=[CH:11][C:10]=1[O:32][CH3:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 11392273DI-Tert-butyl bromomalonateHCID 18398860HCID 18398860, compound

Product 1

HCID 183989737-Benzyloxy-6-methoxy-4-(3,4,5-trimethoxyphenyl)isocoumarin-3-carboxylic acidYield 71.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-benzyloxy-4-methoxy-2-(3,4,5-trimethoxybenzoyl)-benzoic acid (90 g) in dimethylformamide (900 MI) are added potassium carbonate (60.5 g) and di-tert-butyl bromomalonate (64.6 g), and the mixture is stirred at room temperature for three hours. To the reaction mixture are added ethyl acetate and water. The ethyl acetate layer is separated, washed, dried, and concentrated under reduced pressure. To the residue is added a 4M solution of hydrogen chloride in ethyl acetate (500 ml), and the mixture is stirred at room temperature for five hours. The precipitated crystals are collected by filtration, washed, dried, and dissolved in a mixture of acetic acid (40 ml) and dioxane (80 ml). The mixture is heated under reflux for five hours, and the precipitated crystals are collected by filtration. washed, and dried to give 7-benzyloxy-6-methoxy-4-(3,4,5-trimethoxyphenyl)isocoumarin-3-carboxylic acid (70.0 g) as listed in Table 59.

Workup

  1. customThe ethyl acetate layer is separated
  2. washwashed
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. additionTo the residue is added a 4M solution of hydrogen chloride in ethyl acetate (500 ml)
  6. stirringthe mixture is stirred at room temperature for five hours
  7. filtrationThe precipitated crystals are collected by filtration
  8. washwashed
  9. customdried
  10. dissolutiondissolved in a mixture of acetic acid (40 ml) and dioxane (80 ml)
  11. temperatureThe mixture is heated
  12. temperatureunder reflux for five hours
  13. filtrationthe precipitated crystals are collected by filtration
  14. washwashed
  15. customdried

Sources & evidence

ORD record
ord-fb36f78292b646ba8b2aa08b4252d083
Source dataset
uspto-grants-2002_11
Patent number
US06486155B1

Reaction notes

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