Bromine → 2-[(5-Bromopyrimidin-4-yl)methyl]isoindoline-1,3-dione

HRID 2092031Notes

Reaction equation

HRID 2092031 reaction equation
[Br:1][C:2]1[C:3]([CH3:8])=[N:4][CH:5]=[N:6][CH:7]=1.BrBr.[C:11]1(=[O:21])[NH:15][C:14](=[O:16])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.[K]>C(O)(=O)C.C(OCC)(=O)C.O.[OH-].[Na+]>[Br:1][C:2]1[C:3]([CH2:8][N:15]2[C:11](=[O:21])[C:12]3[C:13](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:14]2=[O:16])=[N:4][CH:5]=[N:6][CH:7]=1

Participants

8

Reactant 3

HCID 24408BromineHCID 124618635-Bromo-4-methylpyrimidineHCID 24194345Phthalimide potassium salt

Product 1

HCID 595745872-[(5-Bromopyrimidin-4-yl)methyl]isoindoline-1,3-dioneYield 88.3%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

5-Bromo-4-methylpyrimidine (2.90 g, 16.8 mmol) in acetic acid (40 mL) was stirred with bromine (3.18 g, 20.2 mmol) at 80° C. for 40 minutes. After completion of the reaction, the reaction solution was cooled, diluted with ethyl acetate and neutralized with water and 1 M aqueous sodium hydroxide, and the organic layer was separated, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=7/1). The resulting product (3.69 g) was dissolved in 60 mL of dimethylformamide and heated with potassium phthalimide (2.84 g, 15.3 mmol) at 80° C. for 1 hour with stirring. After completion of the reaction, the reaction solution was mixed with water and extracted with chloroform, and the extract was dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform) to give the desired product (4.3 g, 80% yield).

Workup

  1. customAfter completion of the reaction
  2. temperaturethe reaction solution was cooled
  3. customthe organic layer was separated
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=7/1)
  7. dissolutionThe resulting product (3.69 g) was dissolved in 60 mL of dimethylformamide
  8. customAfter completion of the reaction
  9. extractionextracted with chloroform
  10. dry with materialthe extract was dried over anhydrous magnesium sulfate
  11. customevaporated under reduced pressure
  12. customThe resulting residue was purified by silica gel column chromatography (chloroform)

Sources & evidence

ORD record
ord-8a893667f25944d6b8d7ec4c8e521e35
Source dataset
uspto-grants-2013_05
Patent number
US08440666B2

Reaction notes

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