Malonic Acid → HCID 178524633, compound

HRID 516957Notes

Reaction equation

HRID 516957 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=O.C(O)(=O)[CH2:14][C:15]([OH:17])=[O:16]>C(O)(=O)C.C([O-])(O)=O.[Na+]>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]=[C:6]([OH:11])[CH:5]=[C:14]2[C:15]([OH:17])=[O:16]

Participants

5

Reactant 2

HCID 867Malonic AcidHCID 2365665-Fluoroisatin2×

Product 1

HCID 178524633HCID 178524633, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A stirred suspension of 5-fluoroisatin, also known as 5-fluoro-2,3-indoledione, available from Sigma-Aldrich (10.00 g, 61 mmol) and malonic acid (18.91 g, 182 mmol) in acetic acid (400 ml) was refluxed for 16 h. Acetic acid was removed under reduced pressure, the residue was suspended in water (400 ml), filtered and washed with water (300 ml) to give a brown solid. The solid was stirred in NaHCO3 saturated aqueous solution (800 ml) and the insoluble material was filtered off. The filtrate was acidified to pH 1-2 with concentrated HCl and the resulting precipitate was filtered, washed with water (300 ml) and dried. The resulting pale yellow solid (10 g, Yield 54%) was used directly for synthesis of preparation 4 without further purification. The mixture was analysed by 1H NMR and LCMS: 1H NMR (500 MHz; d6-DMSO) δ 2.08 (s, 1.5 H), 7.01 (s, 1H), 7.35-7.37 (m, 0.5 H)*, 7.48-7.49 (m, 2H), 7.64-7.68 (m, 0.9H)*, 8.01-8.04 (m, 1H), 12.29 (brs, 1H), 13.38 (brs, 0.7H)* ppm.

Workup

  1. temperaturewas refluxed for 16 h
  2. customAcetic acid was removed under reduced pressure
  3. filtrationfiltered
  4. washwashed with water (300 ml)
  5. customto give a brown solid
  6. filtrationthe insoluble material was filtered off
  7. filtrationthe resulting precipitate was filtered
  8. washwashed with water (300 ml)
  9. customdried

Sources & evidence

ORD record
ord-c933b435878f42cf9362579748f65969
Source dataset
uspto-grants-2015_08
Patent number
US09115088B2

Reaction notes

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