6-iodo-8-methyl-2,4-dihydro-1H-3,1-benzoxazine-2,4-dione → 6-cyano-8-methyl-1H-benzo[d][1,3]oxazine-2,4-dione

HRID 1819277Notes

Reaction equation

HRID 1819277 reaction equation
I[C:2]1[CH:13]=[C:12]([CH3:14])[C:5]2[NH:6][C:7](=[O:11])[O:8][C:9](=[O:10])[C:4]=2[CH:3]=1.[C:15]([Cu])#[N:16]>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:14][C:12]1[C:5]2[NH:6][C:7](=[O:11])[O:8][C:9](=[O:10])[C:4]=2[CH:3]=[C:2]([C:15]#[N:16])[CH:13]=1

Participants

5

Reactant 2

HCID 111974156-iodo-8-methyl-2,4-dihydro-1H-3,1-benzoxazine-2,4-dioneHCID 178418546HCID 178418546, compound

Product 1

HCID 578871986-cyano-8-methyl-1H-benzo[d][1,3]oxazine-2,4-dioneYield 61.2%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

600 mg (1.98 mmol) 6-iodo-8-methyl-1H-benzo[d][1,3]oxa zine-2,4-dione (prepared according to known procedures, see G. M. Coppola, Synthesis, 1980, 505), 212 mg (2.37 mmol) CuCN, 377 mg (1.98 mmol) Cul and 114 mg tetrakis(triphenylphosphine) palladium in 60 ml THF are heated 5 h at reflux. After cooling down, the mixture is filtered on Hyflo. The organic phase is washed with water and evaporated. The residue is crystallized from a mixture of dichloromethane, ethyl acetate and hexane to afford 245 mg 8-methyl-2,4-dioxo-1,4-dihydro-2H-benzo[d][1,3]oxazine-6-carbonitrile, which is directly used in the next step.

Workup

  1. temperatureat reflux
  2. temperatureAfter cooling down
  3. filtrationthe mixture is filtered on Hyflo
  4. washThe organic phase is washed with water
  5. customevaporated
  6. customThe residue is crystallized from a mixture of dichloromethane, ethyl acetate and hexane

Sources & evidence

ORD record
ord-763e24c5bd5140198328a398d6ca11c2
Source dataset
uspto-grants-2009_10
Patent number
US07601743B2

Reaction notes

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