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Indoline → 1-(4-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-2,3-dihydro-1H-indole

HRID 1667617
ノート
印刷プレビュー

反応式

HRID 1667617 の反応式
Br[C:2]1[CH:7]=[C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C@@H:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH3:14])[CH:5]=[CH:4][N:3]=1.[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:25][CH2:24]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[K+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O.O>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([C@H:13]([N:9]2[CH2:10][CH2:11][CH2:12][C@H:8]2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([N:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:25][CH2:24]3)[CH:7]=2)[CH3:14])=[CH:16][CH:17]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

HCID 10328IndolineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23665647Potassium tert-butoxideHCID 581118522-Bromo-4-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine

生成物 1

HCID 581119481-(4-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-2,3-dihydro-1H-indole収率 85.5%

試薬・触媒・溶媒

4
HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

To a solution of 2-Bromo-4-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine (0.15 g, 0.41 mmol) in toluene (30 mL) are added indoline (0.10 g, 0.83 mmol), 2-(dicyclohexylphosphino)-biphenyl (14 mg, 0.04 mmol), Pd2(dba)3 (19 mg, 0.02 mmol) and potassium tert-butoxide (0.11 g, 1.04 mmol). The reaction mixture is stirred at 85° C. for 3 h and cooled to room temperature. Water and EtOAc are added to the mixture. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 5%˜25%) to give (1-(4-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-2,3-dihydro-1H-indole (140 mg, 84%) as an oil. M/Z=400.2 [M+1]

後処理

  1. temperaturecooled to room temperature
  2. customThe layers are separated
  3. extractionthe aqueous layer is extracted with EtOAc
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated down
  8. customThe crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 5%˜25%)

出典と根拠

ORDレコード
ord-68c2fcf38305444eb4251c21e1cec851
出典データセット
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08044209B2

反応ノート

読み込み中…

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