Dimethylformamide → 5-cyanophthalimide

HRID 571334Notes

Reaction equation

HRID 571334 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:6][C:5]2=[O:12].[CH3:13][N:14](C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[C-]#N.[Zn+2]>[O:11]=[C:7]1[C:8]2[C:4](=[CH:3][C:2]([C:13]#[N:14])=[CH:10][CH:9]=2)[C:5](=[O:12])[NH:6]1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 2360184-Bromophthalimide

Product 1

HCID 121983335-cyanophthalimideYield 27.4%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
200 °C

Procedure

A mixture of 5-bromoisoindoline-1,3-dione (2.5 g, 11.06 mmol) and Pd(Ph3P)4 (1.406 g, 1.217 mmol) in DMF (50 ml) was accurately degassed with nitrogen, then Zn(CN)2 (1.299 g, 11.06 mmol) was added, and the solution, splitted in 5 vials, was heated under microwave irradiation at 200° C. for 1 hour. A 3% aqueous solution of NH4OH (200 ml) was added, and the organic phase was extracted with ethyl acetate (3×150 ml). The combined organic layers were washed with brine (150 ml), dried over sodium sulfate and concentrated to dryness. The crude was purified by silica gel flash chromatography (100% DCM to DCM:MeOH=99:1) to afford 1,3-dioxoisoindoline-5-carbonitrile as (0.522 g, 3.03 mmol, 27.4% yield, MS/ESI+ 172.9 [MH]+).

Workup

  1. customwas accurately degassed with nitrogen
  2. customthe solution, splitted in 5 vials
  3. additionA 3% aqueous solution of NH4OH (200 ml) was added
  4. extractionthe organic phase was extracted with ethyl acetate (3×150 ml)
  5. washThe combined organic layers were washed with brine (150 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to dryness
  8. customThe crude was purified by silica gel flash chromatography (100% DCM to DCM:MeOH=99:1)

Sources & evidence

ORD record
ord-248d5530493c40ba9f84bc147b95e503
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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