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Pyridine → (1S,2S)-2-[4-((R)-7-Fluoro-4-phenoxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid

HRID 625712
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HRID 625712 반응식
C([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])C.N1C=CC=CC=1.[C:33]1(B(O)O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[NH4+].[OH-]>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:25][C:23]1[CH:22]=[CH:21][C:20]([O:26][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[C:19]2[C:24]=1[C@H:16]([O:15][C:12]1[CH:13]=[CH:14][C:9]([C@H:7]3[CH2:8][C@@H:6]3[C:4]([OH:3])=[O:5])=[CH:10][CH:11]=1)[CH2:17][CH2:18]2
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 1049PyridineHCID 14923Ammonium HydroxideHCID 66827Phenylboronic AcidHCID 118093712(1S,2S)-2-[4-((R)-7-Fluoro-4-hydroxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester2회

생성물 1

HCID 118093716(1S,2S)-2-[4-((R)-7-Fluoro-4-phenoxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid수율 23.5%

시약·촉매·용매

2
HCID 8895Cupric acetate촉매HCID 6344Dichloromethane용매

실험 절차

(1S,2S)-2-[4-((R)-7-Fluoro-4-hydroxy-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester (Intermediate 5, 150 mg, 0.42 mmol), pyridine (dry; 0.133 mL, 1.68 mmol) and phenylboronic acid (308 mg, 2.53 mmol) are suspended in dichloromethane (10 mL), 4 Å molecular sieves and copper(II)acetate (153 mg, 1.52 mmol) are added and the mixture is stirred under oxygen atmosphere at room temperature for 20 h. NH4OH (2 M aqueous solution, 20 mL) is added and the mixture is extracted with dichloromethane. The organic phase is collected, dried over sodium sulfate and concentrated under vacuum. The crude product is purified by flash chromatography (10-100% ethyl acetate in cyclohexane) to give the title compound (Yield: 40 mg). LC (METHOD 9): tR=2.52 min; Mass spectrum (ES+): m/z=405 [M+H]+.

후처리

  1. extractionthe mixture is extracted with dichloromethane
  2. customThe organic phase is collected
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product is purified by flash chromatography (10-100% ethyl acetate in cyclohexane)

출처 및 근거

ORD 기록
ord-7a23061ba52b4d8cabed4ece24c33dde
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09308194B2

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