2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 2-(2-(4-Fluoro-benzyl)-5-(5-chloro-2-(methylthio)pyrimidin-4-yl)thiophen-3-yl)ethanol

HRID 507569노트

반응식

HRID 507569 반응식
C([Li])CCC.[F:6][C:7]1[CH:21]=[CH:20][C:10]([CH2:11][C:12]2[S:13][CH:14]=[CH:15][C:16]=2[CH2:17][CH2:18][OH:19])=[CH:9][CH:8]=1.[Cl:22][C:23]1[CH:24]=[N:25][C:26]([S:29][CH3:30])=[N:27][CH:28]=1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.[OH-].[Na+]>O1CCCC1.O>[F:6][C:7]1[CH:21]=[CH:20][C:10]([CH2:11][C:12]2[S:13][C:14]([C:24]3[C:23]([Cl:22])=[CH:28][N:27]=[C:26]([S:29][CH3:30])[N:25]=3)=[CH:15][C:16]=2[CH2:17][CH2:18][OH:19])=[CH:9][CH:8]=1

참가 물질

8

반응물 5

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 14798Sodium HydroxideHCID 47370635-Chloro-2-(methylthio)pyrimidineHCID 574288302-(2-(4-Fluorobenzyl)thiophen-3-yl)ethanolHCID 178418339Butyllithium

생성물 1

HCID 602044632-(2-(4-Fluoro-benzyl)-5-(5-chloro-2-(methylthio)pyrimidin-4-yl)thiophen-3-yl)ethanol수율 28%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
-78 °C

실험 절차

n-Butyllithium (5.4 mL, 1.6 M in hexanes, 8.63 mmol) was added dropwise to a solution of 2-(2-(4-fluorobenzyl)thiophen-3-yl)ethanol (0.97 g, 4.11 mmol) in anhydrous tetrahydrofuran (15 mL) at −78° C. The resulting mixture was stirred at −78° C. for 1 h and then a solution of 5-chloro-2-(methylthio)pyrimidine (0.79 g, 4.93 mmol) in 1 mL of tetrahydrofuran was added slowly. The mixture was stirred at −78° C. for 1 h and then at −40° C. for 2 h. The reaction was quenched with a solution (1.1 mL) of acetic acid and methanol (1:1) at −40° C. and then a solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.1.1 g, 4.93 mmol) in tetrahydrofuran (1 mL) was added. After complete addition the reaction was stirred at −40° C. for 1 h, then warmed to rt. 10 mL of aqueous sodium hydroxide (2 M) and 50 mL of water were added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (80 mL), dried over anhydrous sodium sulfate and filtered. The solvent was evaporated in vacuo and the product purified by flash chromatography eluting with ethyl acetate/hexane (1:4) to afford the title compound (0.45 g, 28%). MS (M+H)+ 395/397.

후처리

  1. stirringThe mixture was stirred at −78° C. for 1 h
  2. waitat −40° C. for 2 h
  3. customThe reaction was quenched with a solution (1.1 mL) of acetic acid and methanol (1:1) at −40° C.
  4. additionAfter complete addition the reaction
  5. stirringwas stirred at −40° C. for 1 h
  6. temperaturewarmed to rt
  7. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  8. washThe combined organic layers were washed with brine (80 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customThe solvent was evaporated in vacuo
  12. customthe product purified by flash chromatography
  13. washeluting with ethyl acetate/hexane (1:4)

출처 및 근거

ORD 기록
ord-01b52c9df02548bca13060d153729ded
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786132B2

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