Potassium Carbonate → N-(2,2-difluoroethyl)-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-5-formylbenzo[d]isoxazole-3-carboxamide

HRID 245485ノート

反応式

HRID 245485 の反応式
[F:1][CH:2]([F:20])[CH2:3][NH:4][C:5]([C:7]1[C:11]2[CH:12]=[C:13]([CH:18]=[O:19])[C:14](F)=[C:15]([F:16])[C:10]=2[O:9][N:8]=1)=[O:6].C(=O)([O-])[O-].[K+].[K+].[CH3:27][C@H:28]1[O:33][C@H:32]([CH3:34])[CH2:31][NH:30][CH2:29]1>C(#N)CCC.O.[Cl-].[Na+].O.C(OCC)(=O)C>[F:1][CH:2]([F:20])[CH2:3][NH:4][C:5]([C:7]1[C:11]2[CH:12]=[C:13]([CH:18]=[O:19])[C:14]([N:30]3[CH2:29][C@@H:28]([CH3:27])[O:33][C@H:32]([CH3:34])[CH2:31]3)=[C:15]([F:16])[C:10]=2[O:9][N:8]=1)=[O:6]

参加物

8

反応物 3

HCID 11430Potassium CarbonateHCID 11137133trans-2,6-DimethylmorpholineHCID 86658102N-(2,2-Difluoroethyl)-6,7-difluoro-5-formylbenzo[d]isoxazole-3-carboxamide2 回

生成物 1

HCID 86658101N-(2,2-difluoroethyl)-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-5-formylbenzo[d]isoxazole-3-carboxamide

試薬・触媒・溶媒 4

HCID 962Water溶媒2 回HCID 8008Butyronitrile溶媒HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
90 °C

実験手順

N-(2,2-Difluoroethyl)-6,7-difluoro-5-formylbenzo[d]isoxazole-3-carboxamide (Intermediate 243, 2.86 g, 9.86 mmol) was dissolved in butyronitrile (50 mL) and water (2.5 mL). Potassium carbonate (1.362 g, 9.86 mmol) and (2R,6R)-2,6-dimethylmorpholine (1.481 mL, 11.83 mmol) were added and the reaction was stirred at 90° C. for 4 hours. The crude reaction mixture was diluted with water, brine and ethyl acetate. The mixture was washed 2× with brine. The aqueous layer was back-extracted with ethyl acetate. The organic layers combined, dried over MgSO4 and concentrated. The residue was dissolved in DCM and purified by silica gel column chromatography using a gradient of DCM to ethyl acetate. Fractions were combined and concentrated to give the title compound.

後処理

  1. customThe crude reaction mixture
  2. washThe mixture was washed 2× with brine
  3. extractionThe aqueous layer was back-extracted with ethyl acetate
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in DCM
  7. custompurified by silica gel column chromatography
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-b375496b89b847acaa79fd3891e66005
出典データセット
uspto-grants-2014_02
特許番号
US08658641B2

反応ノート

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