Methyl iodide → 8-fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione

HRID 2244367ノート

反応式

HRID 2244367 の反応式
[F:1][C:2]1[C:7]2[NH:8][C:9](=[O:13])[O:10][C:11](=[O:12])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:14]([O-])([O-])=O.[Na+].[Na+].CI>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[C:7]2[N:8]([CH3:14])[C:9](=[O:13])[O:10][C:11](=[O:12])[C:6]=2[CH:5]=[CH:4][CH:3]=1

参加物

6

反応物 3

HCID 6328Methyl iodideHCID 10340Sodium CarbonateHCID 105353938-Fluoroisatoic anhydride

生成物 1

HCID 866152368-fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione収率 88.5%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 8-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (200 mg, 1.10 mmol) in DMF (2 ml) was added Na2CO3 (129 mg, 1.22 mmol), followed by methyl iodide (104 μl, 1.66 mmol) and the reaction mixture was stirred at RT for 18 h. The reaction mixture was diluted with ethyl acetate and the mixture was washed with water and brine. The organic phase was dried (MgSO4), filtered and concentrated in vacuo to give 8-fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (190 mg, 88%) which was not purified due to its poor solubility but directly used in the following step without further purification. To a suspension of the residue (190 mg, 0.97 mmol) in ethanol (4 ml) was added DMAP (12 mg, 0.09 mmol) and the reaction mixture was heated to reflux for 3 h. The reaction mixture was cooled to RT and then concentrated in vacuo to give a residue which was partitioned between ethyl acetate and 0.1M HCl solution. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography to give the desired product (132 mg, 69%) as a light yellow oil. 1H NMR (CDCl3, 300 MHz): 7.69 (aptd, J=8.0 Hz, 1H), 7.50 (brds, 1H), 7.08 (ddd, J=14.0, 8.0, 1.5 Hz, 1H), 6.51 (aptdt, J=8.0, 4.5 Hz, 1H), 4.31 (q, J=7.0 Hz, 2H), 3.12 (m, 3H), 1.37 (t, J=7.0 Hz, 3H).

後処理

  1. washthe mixture was washed with water and brine
  2. dry with materialThe organic phase was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-1ff0a0e9e92d48bdb543bec89d42cacd
出典データセット
uspto-grants-2010_03
特許番号
US07678818B2

反応ノート

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