Morpholine → HCID 86699759、化合物

HRID 515194ノート

反応式

HRID 515194 の反応式
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:48]1[CH:64]=[C:63]([O:65][CH3:66])[C:51]([C:52]([NH:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][CH:57]=2)=[O:53])=[C:50]([F:67])[CH:49]=1.[NH:68]1[CH2:73][CH2:72][O:71][CH2:70][CH2:69]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:62][C:59]1[CH:60]=[CH:61][C:56]([CH2:55][NH:54][C:52](=[O:53])[C:51]2[C:63]([O:65][CH3:66])=[CH:64][C:48]([N:68]3[CH2:73][CH2:72][O:71][CH2:70][CH2:69]3)=[CH:49][C:50]=2[F:67])=[CH:57][CH:58]=1

参加物

8

反応物 4

HCID 8083MorpholineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86699758HCID 86699758、化合物

生成物 1

HCID 86699759HCID 86699759、化合物収率 42.6%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
120 °C

実験手順

2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (468 mg, 0.75 mmol) is added to a stirred solution of 4-bromo-N-[(4-chlorophenyl)-methyl]-2-fluoro-6-methoxy-benzamide (2.8 g, 7.52 mmol), morpholine (0.92 g, 10.5 mmol) and sodium tert-butoxide (0.94 g, 9.78 mmol) in toluene (90 ml) and the mixture is degassed and flushed with argon for 45 min. Tris(dibenzylideneacetone)-dipalladium(0) (344 mg, 0.38 mmol) is added and the mixture is heated at 120° C. for 16 h. The mixture is cooled to room temperature and diluted with water (50 ml). The mixture is extracted with ethyl acetate (2×30 ml). The combined organic layers are washed with water (30 ml), brine (40 ml), dried over anhydrous sodium sulfate and evaporated to get the crude which is purified by column chromatography (silica gel, 5% ethyl acetate/dichloromethane) to yield N-[(4-chlorophenyl)-methyl]-2-fluoro-6-methoxy-4-morpholin-4-yl-benzamide (1.3 g, 3.2 mmol, 33%).

後処理

  1. customthe mixture is degassed
  2. customflushed with argon for 45 min
  3. temperatureThe mixture is cooled to room temperature
  4. extractionThe mixture is extracted with ethyl acetate (2×30 ml)
  5. washThe combined organic layers are washed with water (30 ml), brine (40 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customto get the crude which
  9. customis purified by column chromatography (silica gel, 5% ethyl acetate/dichloromethane)

出典と根拠

ORDレコード
ord-99c16311cd5f4bf3abafe82c16ed8bf9
出典データセット
uspto-grants-2015_08
特許番号
US09108936B2

反応ノート

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