Sodium Hydroxide → 6-[2-Fluoro-4-(methylsulfonyl)phenyl]-3-pyridinol

HRID 423532노트

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HRID 423532 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[C:4]([F:15])[CH:3]=1.[Na+].[CH3:17][S:18]([O-:20])=[O:19].[OH-].[Na+]>CS(C)=O>[F:15][C:4]1[CH:3]=[C:2]([S:18]([CH3:17])(=[O:20])=[O:19])[CH:7]=[CH:6][C:5]=1[C:8]1[N:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1

참가 물질

5

반응물 3

HCID 14798Sodium HydroxideHCID 2733271Sodium methanesulfinateHCID 666732076-(4-Bromo-2-fluorophenyl)-3-pyridinol

생성물 1

HCID 666730256-[2-Fluoro-4-(methylsulfonyl)phenyl]-3-pyridinol수율 68.3%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
120 °C

실험 절차

A mixture of 6-(4-bromo-2-fluorophenyl)-3-pyridinol (0.245 g, 0.91 mmol), methanesulfinic acid sodium salt (0.47 g, 80%, 3.66 mmol), Cul (0.70 g, 3.66 mmol) and NaOH (44 mg, 1.10 mmol) in DMSO (20 mL) was degassed with N2 three times and heated at 120° C. overnight. After the mixture was cooled to ambient temperature, 1N HCl was added to adjust the aqueous pH to about 8. The mixture was extracted with EtOAc. The combined organic extract was washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a light brown viscous oil. The crude product was purified by chromatography on a silica gel column eluted with 2:4:0.1 EtOAc/CH2Cl2/MeOH to give 0.166 g (68%) of 6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinol as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.26 (d, 1H, J=2.7 Hz), 8.15-8.05 (m, 1H), 7.90-7.75 (m, 2H), 7.74 (dd, 1H, Ja=8.6 Hz, Jb=2.1 Hz), 7.32 (dd, 1H, Ja=8.6 Hz, Jb=2.8 Hz), 3.18 (s, 3H); LRMS (ESI), m/z 268 (M+H).

후처리

  1. customwas degassed with N2 three times
  2. temperatureAfter the mixture was cooled to ambient temperature
  3. addition1N HCl was added
  4. extractionThe mixture was extracted with EtOAc
  5. extractionThe combined organic extract
  6. washwas washed with water and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated
  10. customto give the crude product as a light brown viscous oil
  11. customThe crude product was purified by chromatography on a silica gel column
  12. washeluted with 2:4:0.1 EtOAc/CH2Cl2/MeOH

출처 및 근거

ORD 기록
ord-706382dcd4e54699973aeaa778417975
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101634B2

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