Water → HCID 68514021, compound

HRID 1512984Notes

Reaction equation

HRID 1512984 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[C:11]1(=O)[O:16][C:14](=[O:15])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.O>CN(C)C=O>[F:1][C:2]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:3]=1[N:4]1[C:14](=[O:15])[C:13]2[C:12](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:11]1=[O:16]

Participants

5

Reactant 3

HCID 962WaterHCID 6811Phthalic AnhydrideHCID 37563832-Fluoro-4-methoxyaniline

Product 1

HCID 68514021HCID 68514021, compoundYield 78.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 2-fluoro-4-methoxyaniline (2.22 g) and phthalic anhydride (2.33 g) in N,N-dimethylformamide (16 mL) was stirred at 120° C. for 1 hour. The reaction mixture was cooled to room temperature. To the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residual crystals were suspended in ethyl acetate (5 mL), and the suspension was stirred at room temperature for 10 minutes. To the suspension was added n-hexane (25 mL), and the crystals were collected by filtration. The collected crystals were dried under reduced pressure to give 3-fluoro-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)anisole (3.35 g). This material was suspended in 1,2-dichloroethane (12.4 mL). To the suspension was added chlorosulfonic acid (1.81 mL) in a dropwise manner under ice-cooling, and the mixture was heated at reflux for 1 hour. The reaction mixture was cooled to room temperature. To the reaction mixture were added thionyl chloride (4.5 mL) and N,N-dimethylformamide (0.048 mL), and the mixture was heated at reflux for 2 hours. The reaction mixture was cooled to room temperature, and diluted with ethyl acetate. To the mixture was added water, and the organic layer was separated. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residual crystals were suspended in ethyl acetate (10 mL). To the suspension was added n-hexane (30 mL), and the crystals were collected by filtration. The collected crystals were washed with n-hexane, and dried under reduced pressure to give the title compound (3.6 g).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe extract was washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was removed under reduced pressure
  6. stirringthe suspension was stirred at room temperature for 10 minutes
  7. additionTo the suspension was added n-hexane (25 mL)
  8. filtrationthe crystals were collected by filtration
  9. customThe collected crystals were dried under reduced pressure

Sources & evidence

ORD record
ord-1e4de6b3f20b43f8987b1d1d76ed14a3
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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