Cesium carbonate → 7-Chloro-6-(3-phenylazetidin-1-yl)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1013117ノート

反応式

HRID 1013117 の反応式
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[C:27]1([CH:33]2[CH2:36][NH:35][CH2:34]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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].C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[N:35]1[CH2:36][CH:33]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:34]1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 289015863-PhenylazetidineHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

生成物 1

HCID 597990437-Chloro-6-(3-phenylazetidin-1-yl)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine収率 35%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
95 °C

実験手順

Use 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (prepared essentially as described in Preparation 1) (183 mg, 0.43 mmol), 3-phenylazetidine (75.2 mg, 0.56 mmol), palladium (II) acetate) (9.0 mg, 0.04 mmol), tris(dibenzylideneacetone)dipalladium(0) (37 mg, 0.04 mmol), BINAP (racemic, 37 mg, 0.06 mmol), cesium carbonate (195 mg, 0.6 mmol), anhydrous toluene (10 mL) and degas and fill with nitrogen (3 times). Seal the system with septum and tighten it with copper wire when necessary. Heat the mixture at 95° C. for 8 h. Dilute with EtOAc, wash with saturated aqueous sodium bicarbonate solution, brine, dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 10:90 EtOAc:hexanes) to give the title compound (61 mg, 35%).

後処理

  1. customdegas
  2. customSeal the system with septum
  3. additionDilute with EtOAc
  4. washwash with saturated aqueous sodium bicarbonate solution, brine
  5. dry with materialdry (sodium sulfate)
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 10:90 EtOAc:hexanes)

出典と根拠

ORDレコード
ord-917e5fef252447158c401ba2de1ca585
出典データセット
uspto-grants-2011_07
特許番号
US07981882B2

反応ノート

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