Sodium Bicarbonate → 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol

HRID 595645노트

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HRID 595645 반응식
C(OC([N:8]1[C:16]2[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1B(O)O)=O)(C)(C)C.[Cl:21][C:22]1[N:27]=[C:26](I)[C:25]([OH:29])=[CH:24][CH:23]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.O.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:21][C:22]1[N:27]=[C:26]([C:9]2[NH:8][C:16]3[C:11]([CH:10]=2)=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=3)[C:25]([OH:29])=[CH:24][CH:23]=1

참가 물질

8

반응물 3

HCID 516892Sodium BicarbonateHCID 234331586-Chloro-2-iodo-3-hydroxypyridineHCID 44118245(1-(tert-Butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid

생성물 1

HCID 867262926-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol수율 72,026.297%

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

To a solution of (1-(tert-butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid (126 g, 0.45 mol) and 6-chloro-2-iodopyridin-3-ol (96 g, 0.37 mmol) in 1,4-dioxane (1.8 L) and water (0.2 L) were added Pd(PPh3)2Cl2 (13.2 g, 18.6 mmol) and NaHCO3 (94.8 g, 1.13 mol) under nitrogen atmosphere, and the mixture was heated at 90° C. under N2 for 16 h. The reaction mixture was cooled to room temperature, diluted with EtOAc (900 mL), filtered and concentrated. The residue was diluted with H2O (400 mL) and EtOAc (800 mL), and the layer was separated, the aqueous layer was extracted with EtOAc (3*400 mL). The combined organic layers were washed with brine (800 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (PE:EtOAc=20:1˜3:1) to give 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol (70 g, yield: 70.1%). 1H-NMR (MeOD, 400 MHz) δ 7.36 (s, 1H), 7.23˜7.27 (m, 2H), 7.03˜7.11 (m, 2H), 6.63˜6.68 (m, 1H). MS (M+H)+: 263 (M+H).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated
  4. additionThe residue was diluted with H2O (400 mL) and EtOAc (800 mL)
  5. customthe layer was separated
  6. extractionthe aqueous layer was extracted with EtOAc (3*400 mL)
  7. washThe combined organic layers were washed with brine (800 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by column chromatography (PE:EtOAc=20:1˜3:1)

출처 및 근거

ORD 기록
ord-8ee2406763c54b50b3b4ce7c1ba3809b
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09243002B2

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