Sulfuric Acid → 1H-Isoindol-3-amine, 5,6-diethoxy-4-fluoro-, sulfate (1:1)

HRID 732249Notes

Reaction equation

HRID 732249 reaction equation
[CH2:1]([O:3][C:4]1[C:5]([F:17])=[C:6]([C:15]#[N:16])[C:7](=[CH:10][C:11]=1[O:12][CH2:13][CH3:14])[C:8]#[N:9])[CH3:2].[S:18](=[O:22])(=[O:21])([OH:20])[OH:19].C(N(CC)CC)C>[OH-].[Pd+2].[OH-].[C].COCCOC>[S:18]([OH:22])([OH:21])(=[O:20])=[O:19].[CH2:13]([O:12][C:11]1[CH:10]=[C:7]2[C:6](=[C:5]([F:17])[C:4]=1[O:3][CH2:1][CH3:2])[C:15]([NH2:16])=[N:9][CH2:8]2)[CH3:14]

Participants

6

Reactant 3

HCID 1118Sulfuric Acid2×HCID 8471TriethylamineHCID 229298414,5-Diethoxy-3-fluorophthalonitrile

Product 1

HCID 115880541H-Isoindol-3-amine, 5,6-diethoxy-4-fluoro-, sulfate (1:1)Yield 72%

Reagents, catalysts & solvents 2

HCID 178502593HCID 178502593, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-23 °C

Procedure

A mixture of 4,5-diethoxy-3-fluorophthalonitrile (2.34 g, 10 mol) prepared in Preparation Example 1, sulfuric acid (0.56 mL, 10 mol), 20% palladium hydroxide-carbon (0.59 g, 50% hydrate) (20% palladium-carbon powder, palladium hydroxide type (hydrate), N.E. Chemical Corporation) and 1,2-dimethoxyethane (23 mL) was stirred at −23° C. under hydrogen atmosphere (atmospheric pressure) for 29 hours. After insoluble matter in the reaction mixture was filtered off, the residue was washed with methanol (23 mL), and the combined filtrate was divided into five equal portions. To one of them, triethylamine (0.14 mL, 1 mol) was added, and the mixture was stirred at 60° C. for three hours and concentrated at 40° C. under reduced pressure. Methanol (2.3 mL) and 1,2-dimethoxyethane (6.9 mL) were added to the residue, then sulfuric acid (0.11 mL, 2 mol) was added on ice, and the mixture was stirred. Precipitated crystals were filtered, washed with a 5% methanol-1,2-dimethoxyethane solution, and dried at room temperature under reduced pressure to give 0.45 g of the title compound (yield: 72%) as grayish white crystals.

Workup

  1. filtrationAfter insoluble matter in the reaction mixture was filtered off
  2. washthe residue was washed with methanol (23 mL)
  3. stirringthe mixture was stirred at 60° C. for three hours
  4. concentrationconcentrated at 40° C. under reduced pressure
  5. additionMethanol (2.3 mL) and 1,2-dimethoxyethane (6.9 mL) were added to the residue
  6. stirringthe mixture was stirred
  7. customPrecipitated crystals
  8. filtrationwere filtered
  9. washwashed with a 5% methanol-1,2-dimethoxyethane solution
  10. customdried at room temperature under reduced pressure

Sources & evidence

ORD record
ord-71d5a13e2cff468781edfaff52249ccd
Source dataset
uspto-grants-2009_09
Patent number
US07585982B2

Reaction notes

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