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Cesium carbonate → (1S,2S)-2-{4-[(R)-4-(4-Cyano-phenoxy)-7-fluoro-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester

HRID 625695
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HRID 625695 반응식
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([OH:26])[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:11][CH:10]=1)=[O:5])[CH3:2].F[C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:10]=[CH:11][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([O:26][C:28]4[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=4)[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:13][CH:14]=1)=[O:5])[CH3:2]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 145174-FluorobenzonitrileHCID 118093712(1S,2S)-2-[4-((R)-7-Fluoro-4-hydroxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester2회

생성물 1

HCID 118093725(1S,2S)-2-{4-[(R)-4-(4-Cyano-phenoxy)-7-fluoro-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester수율 33.1%

시약·촉매·용매 2

HCID 962
Water
용매
HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

(1S,2S)-2-[4-((R)-7-Fluoro-4-hydroxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester (Intermediate 5, 146 mg, 0.41 mmol), 4-fluorobenzonitrile (55 mg, 0.45 mmol), and cesium carbonate (145 mg, 0.45 mmol) are suspended in dry dimethylformamide (10 mL) and stirred for 3 hours at 100° C. followed by room temperature overnight. The mixture is diluted with water and extracted with ethyl acetate. The organic extract is dried over sodium sulfate, filtered and the solvent removed. The residue is purified by flash chromatography (10% ethyl acetate in cyclohexane) to give the title compound (Yield 62 mg). LC (METHOD 5): tR=1.54 min; Mass spectrum (ES+): m/z=458 [M+H]+.

후처리

  1. waitfollowed by room temperature overnight
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. dry with materialis dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent removed
  7. customThe residue is purified by flash chromatography (10% ethyl acetate in cyclohexane)

출처 및 근거

ORD 기록
ord-c98f214efd9d4626aae482d7647e4705
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09308194B2

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