Sodium sulfate decahydrate → HCID 131721514, compound

HRID 612474Notes

Reaction equation

HRID 612474 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[ClH:7].[F:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[C:14](=O)[N:13]([NH:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1)[C:12]2=O.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1>[ClH:7].[F:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[CH2:14][N:13]([NH:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1)[CH2:12]2

Participants

5

Reactant 3

HCID 62649Sodium sulfate decahydrateHCID 19595216HCID 19595216, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 131721514HCID 131721514, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-fluorophthalic anhydride (5.99 g), 4-pyridinylhydrazine hydrochloride (5.00 g), and glacial acetic (30 ml) acid was stirred under reflux, under nitrogen, for 4 hrs. The reaction mixture was evaporated, and the residue was azeotroped with heptane. The residue was dried in vacuo to give 4-fluoro-2-(4-pyridinylamino)-isoindol-1,3-dione. To a mixture of lithium aluminum hydride (3.91 g) and dry tetrahydrofuran (100 ml), 2,3-dihydro-5-fluoro-2-(4-pyridinylamino)isoindole-1,3-dione hydrochloride was added in portions with rapid stirring, under nitrogen, at ambient temperature. The reaction mixture was stirred under nitrogen, overnight, at ambient temperature, and sodium sulfate decahydrate was added in portions. The mixture was filtered through a bed of celite, the filter cake was washed with ethyl acetate and concentrated in vacuo. The residue was chromatographed over silica gel, eluting with 7% methanol-dichloromethane, followed by 185:14:1 dichloromethane:methanol:ammonium hydroxide. The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol, excess concentrated hydrochloric acid was added, and the mixture was evaporated. The residue was crystallized from absolute ethanol to give 550 mg (6%) of product, (dried under vacuum at 80° C. overnight), mp 235-240° C. (decomp).

Workup

  1. additionwas added in portions with rapid stirring, under nitrogen, at ambient temperature
  2. filtrationThe mixture was filtered through a bed of celite
  3. washthe filter cake was washed with ethyl acetate
  4. concentrationconcentrated in vacuo
  5. customThe residue was chromatographed over silica gel
  6. washeluting with 7% methanol-dichloromethane
  7. customThe appropriate fractions were collected
  8. customevaporated
  9. dissolutionThe residue was dissolved in absolute ethanol
  10. additionexcess concentrated hydrochloric acid was added
  11. customthe mixture was evaporated
  12. customThe residue was crystallized from absolute ethanol

Sources & evidence

ORD record
ord-298e649bf73244958d84b2b912cdf353
Source dataset
uspto-grants-1999_12
Patent number
US06004977

Reaction notes

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