Morpholine → HCID 86699759, 화합물

HRID 515194노트

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HRID 515194 반응식
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

참가 물질

8

반응물 4

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

생성물 1

HCID 86699759HCID 86699759, 화합물수율 42.6%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매

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온도
120 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-99c16311cd5f4bf3abafe82c16ed8bf9
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108936B2

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