(Diethylamino)sulfur trifluoride → Dimethyl 5-fluoromethylisophthalate

HRID 473235Notes

Reaction equation

HRID 473235 reaction equation
O[CH2:2][C:3]1[CH:4]=[C:5]([C:13]([O:15][CH3:16])=[O:14])[CH:6]=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9].C(N(S(F)(F)[F:23])CC)C>C(Cl)Cl>[F:23][CH2:2][C:3]1[CH:4]=[C:5]([C:13]([O:15][CH3:16])=[O:14])[CH:6]=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9]

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 13907324Dimethyl 5-(hydroxymethyl)isophthalate

Product 1

HCID 67254949Dimethyl 5-fluoromethylisophthalateYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under Ar atmosphere, with ice-cooled, to a solution of dimethyl 5-hydroxymethylisophthalate (32) (3.36 g, 15.0 mmol) in CH2Cl2 (150 mL, 0.1 M solution) was slowly added dropwise (diethylamino)sulfur trifluoride (4.00 mL, 30.5 mmol), and stirred for 2 hours at a room temperature. TLC was used to confirm the progress of the reaction. Then, the reaction was quenched with MeOH (150 mL). The solvent was removed under reduced pressure. The residue was subjected to extraction with EtOAc and a saturated sodium hydrogen carbonate aqueous solution (three times). 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=10:1) to isolate dimethyl 5-fluoromethylisophthalate (33) (2.57 g, 78%) as white crystals.

Workup

  1. customthe progress of the reaction
  2. customThen, the reaction was quenched with MeOH (150 mL)
  3. customThe solvent was removed under reduced pressure
  4. extractionThe residue was subjected to extraction with EtOAc
  5. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated under reduced pressure
  8. customto remove the solvent
  9. customThe residue was purified by neutral silica gel column chromatography (hexane:EtOAc=10:1)

Sources & evidence

ORD record
ord-f8ba0628382f48d48f715655aed4e2c2
Source dataset
uspto-grants-2014_01
Patent number
US08633304B2

Reaction notes

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