Methyl iodide → 5-chloro-6-fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione

HRID 2244371Notes

Reaction equation

HRID 2244371 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:13]2[C:12](=[O:14])[O:11][C:10](=[O:15])[NH:9][C:8]=2[CH:7]=[CH:6][C:5]=1[F:16].[CH3:17]I>CN(C=O)C>[Cl:3][C:4]1[C:13]2[C:12](=[O:14])[O:11][C:10](=[O:15])[N:9]([CH3:17])[C:8]=2[CH:7]=[CH:6][C:5]=1[F:16]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 536626896-Chloro-5-fluoroisatoic acid anhydride

Product 1

HCID 866152375-chloro-6-fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dioneYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of NaH (49 mg, 1.11 mmol) in DMF (2 ml) at RT was added a solution of 5-chloro-6-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (synthesized in analogy to a procedure described in EP 59391) (200 mg, 0.93 mmol) in DMF (2 ml). The mixture was stirred at RT for 1 h and then methyl iodide (87 μl, 1.39 mmol) was added. The reaction mixture was then warmed up to RT and stirring was continued overnight. The mixture was quenched with water and extracted with ether. The organic phase was washed with water and brine, dried (MgSO4), filtered, and concentrated in vacuo to give a residue which was purified by flash column chromatography (1:1 ethyl acetate:cyclohexane) to give the desired compound (83 mg, 39%) as a light yellow solid. 1H NMR (CDCl3, 300 MHz): 7.56 (dd, J=9.5, 8.0 Hz, 1H), 7.10 (dd, J=9.5, 4.0 Hz, 1H), 3.59 (s, 3H).

Workup

  1. customsynthesized in analogy to a procedure
  2. temperatureThe reaction mixture was then warmed up to RT
  3. stirringstirring
  4. waitwas continued overnight
  5. customThe mixture was quenched with water
  6. extractionextracted with ether
  7. washThe organic phase was washed with water and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a residue which
  12. customwas purified by flash column chromatography (1:1 ethyl acetate:cyclohexane)

Sources & evidence

ORD record
ord-37a28c7c943a47a3b72da1e917a5277a
Source dataset
uspto-grants-2010_03
Patent number
US07678818B2

Reaction notes

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