Methyl iodide → Dimethyl 3-hydroxyphthalate

HRID 709586Notes

Reaction equation

HRID 709586 reaction equation
[OH:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:4]2[C:5]([O:7][C:8](=[O:9])[C:3]=12)=[O:6].[C:13](=[O:16])(O)[O-].[Na+].I[CH3:19]>CO.CN(C=O)C>[CH3:13][O:16][C:5](=[O:6])[C:4]1[C:3](=[C:2]([OH:1])[CH:12]=[CH:11][CH:10]=1)[C:8]([O:7][CH3:19])=[O:9]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 965803-Hydroxyphthalic anhydrideHCID 516892Sodium Bicarbonate

Product 1

HCID 12223651Dimethyl 3-hydroxyphthalateYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A stirred mixture of 3-hydroxyphthalic anhydride (20.5 g, 125 mmol) in methanol (100 mL) was heated to reflux for three hours. The solvent was evaporated in vacuo, and the residue was suspended in sodium bicarbonate (29.4 g, 350 mmol) in DMF (250 mL), followed by addition of iodomethane (19 mL, 300 mmol) and heating at 55° C. for four hours. The mixture was cooled to room temperature, solvent evaporated in vacuo, and the residue was partitioned between water (200 mL) and ethyl acetate (200 mL). The organic layer was washed with water (2×200 mL), dried, concentrated in vauco, and then purified by flash column chromatography (Silica Gel, EtOAc/Hexane, 0% gradient to 100% 30 min) to give 3-hydroxyphthalic acid dimethyl ester (20.2 g, 77% yield). The product was used in the next step without further purification.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for three hours
  3. customThe solvent was evaporated in vacuo
  4. temperatureThe mixture was cooled to room temperature
  5. customsolvent evaporated in vacuo
  6. customthe residue was partitioned between water (200 mL) and ethyl acetate (200 mL)
  7. washThe organic layer was washed with water (2×200 mL)
  8. customdried
  9. concentrationconcentrated in vauco
  10. custompurified by flash column chromatography (Silica Gel, EtOAc/Hexane, 0% gradient to 100% 30 min)

Sources & evidence

ORD record
ord-25bf5785d1d6488693f3410c67ad2249
Source dataset
uspto-grants-2015_11
Patent number
US09181216B2

Reaction notes

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