Methanol → Dimethyl 5-(hydroxymethyl)isophthalate

HRID 473234Notes

Reaction equation

HRID 473234 reaction equation
[C:1]1([C:15]([O:17][CH3:18])=[O:16])[CH:6]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[CH:4]=[C:3]([C:11](OC)=[O:12])[CH:2]=1.[BH4-].[Na+].CO>C1COCC1>[OH:12][CH2:11][C:3]1[CH:4]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[CH:6]=[C:1]([CH:2]=1)[C:15]([O:17][CH3:18])=[O:16]

Participants

5

Reactant 3

HCID 887MethanolHCID 75881Trimethyl benzene-1,3,5-tricarboxylateHCID 4311764Sodium borohydride

Product 1

HCID 13907324Dimethyl 5-(hydroxymethyl)isophthalateYield 61.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Trimethyl 1,3,5-benzenetricarboxylate (5.02 g, 19.9 mmol) was dissolved in THF (15 mL). The air was evacuated from the reaction system, and then Ar was charged therein. To the solution were added NaBH4 (901 mg, 23.8 mmol), and then a mixed solution of THF:MeOH (12.5 mL:3.7 mL) slowly dropwise. The reaction mixture was refluxed for 30 minutes. TLC was used to confirm the progress of the reaction. Then, the reaction was quenched with HCl (1 N, 20 mL). The mixture was extracted with EtOAc. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the solvent. The residue was purified by neutral silica gel column chromatography (hexane:EtOAc=4:1 to 3:1) to isolate dimethyl 5-hydroxymethylisophthalate (32) (2.73 g, 61%) as white crystals.

Workup

  1. customThe air was evacuated from the reaction system
  2. additionAr was charged
  3. temperatureThe reaction mixture was refluxed for 30 minutes
  4. customthe progress of the reaction
  5. customThen, the reaction was quenched with HCl (1 N, 20 mL)
  6. extractionThe mixture was extracted with EtOAc
  7. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  8. dry with materialdried over anhydrous sodium sulfate
  9. customevaporated under reduced pressure
  10. customto remove the solvent
  11. customThe residue was purified by neutral silica gel column chromatography (hexane:EtOAc=4:1 to 3:1)

Sources & evidence

ORD record
ord-022365251f784f2ea9a07cd7e9ff0fca
Source dataset
uspto-grants-2014_01
Patent number
US08633304B2

Reaction notes

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