Methyl iodide → 2H-3,1-Benzoxazine-2,4(1H)-dione, 6-chloro-1-methyl-

HRID 2223070Notes

Reaction equation

HRID 2223070 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[NH:12][C:11](=[O:13])[O:10][C:9](=[O:14])[C:8]=2[CH:15]=1.[CH3:16]I>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[N:12]([CH3:16])[C:11](=[O:13])[O:10][C:9](=[O:14])[C:8]=2[CH:15]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 784805-Chloroisatoic anhydride

Product 1

HCID 267242H-3,1-Benzoxazine-2,4(1H)-dione, 6-chloro-1-methyl-

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

As illustrated in the scheme above, NaH (2.43 g of a 60% dispersion, 60.8 mmol) was added to a solution of 6-chloro-2H-3,1-benzoxazine-2,4(1H)-dione (10.0 g, 50.6 mmol) dissolved in DMF (200 mL). The resulting mixture was stirred at room temperature for 30 min., and then methyl iodide (6.3 mL, 101 mmol) was added dropwise. After the reaction had stirred at room temperature overnight, it was concentrated in vacuo. Water and brine were added to the residue, and the aqueous layer was extracted with CH2Cl2 (2×). The combined organic phases were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was triturated with 3:1 hexanes:EtOAc. The solvent was removed by filtration, and the resulting solid was washed with additional 3:1 hexanes:EtOAc, followed by 100% hexanes. The product was dried briefly under vacuum to produce the title compound as a pale yellow solid. (8.59 g, 80%). 1H-NMR (DMSO-d6): δ 7.96 (d, J=2.6 Hz, 1H), 7.89 (dd, J=2.6 Hz, J=9.0 Hz, 1H), 7.48 (d, J=9.0 Hz, 1H), 3.45 (s, 3H). MS (ESI) (M+H)+=212.

Workup

  1. stirringAfter the reaction had stirred at room temperature overnight
  2. concentrationit was concentrated in vacuo
  3. additionWater and brine were added to the residue
  4. extractionthe aqueous layer was extracted with CH2Cl2 (2×)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was triturated with 3:1 hexanes
  9. customThe solvent was removed by filtration
  10. washthe resulting solid was washed with additional 3:1 hexanes
  11. customThe product was dried briefly under vacuum

Sources & evidence

ORD record
ord-8afd750bc81a4b1f9e6238c7fc637626
Source dataset
uspto-grants-2008_05
Patent number
US07375101B2

Reaction notes

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