2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 2-Chloro-4-(5-tosylthiophen-2-yl)pyrimidine

HRID 507558Notes

Reaction equation

HRID 507558 reaction equation
C([Li])CCC.[S:6]([C:16]1[S:17][CH:18]=[CH:19][CH:20]=1)([C:9]1[CH:15]=[CH:14][C:12]([CH3:13])=[CH:11][CH:10]=1)(=[O:8])=[O:7].[Cl:21][C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.[OH-].[Na+]>O1CCCC1>[Cl:21][C:22]1[N:27]=[C:26]([C:18]2[S:17][C:16]([S:6]([C:9]3[CH:10]=[CH:11][C:12]([CH3:13])=[CH:14][CH:15]=3)(=[O:7])=[O:8])=[CH:20][CH:19]=2)[CH:25]=[CH:24][N:23]=1

Participants

7

Reactant 5

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 14798Sodium HydroxideHCID 744042-ChloropyrimidineHCID 2555212-TosylthiopheneHCID 178418339Butyllithium

Product 1

HCID 602044282-Chloro-4-(5-tosylthiophen-2-yl)pyrimidineYield 49.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium in hexanes (0.92 mL, 2.5 M, 2.30 mmol) was added dropwise to a solution of 2-tosylthiophene (0.5 g, 2.09 mmol) in anhydrous tetrahydrofuran (30 mL) at −78° C. The resulting mixture was stirred at −78° C. for 1 h and a solution of 2-chloropyrimidine (0.26 g, 2.30 mmol) in 3 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 (0.22 mL) of acetic acid and methanol (1:1) at −40° C. and a solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.57 g, 2.51 mmol) was added. After complete addition the reaction was stirred for 1 h, and then warmed to rt and stirred for an additional 15 h. 20 mL of aqueous sodium hydroxide (2 M) was added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (80 mL), dried over anhydrous sodium sulfate and filtered. The solvent was evaporated in vacuo and the product was purified by flash chromatography eluting with ethyl acetate/hexane (1:3) to afford the title compound as a white solid (0.36 g, 49%).

Workup

  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 (0.22 mL) of acetic acid and methanol (1:1) at −40° C.
  4. additionAfter complete addition the reaction
  5. stirringwas stirred for 1 h
  6. temperaturewarmed to rt
  7. stirringstirred for an additional 15 h
  8. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  9. washThe combined organic layer was washed with brine (80 mL)
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customThe solvent was evaporated in vacuo
  13. customthe product was purified by flash chromatography
  14. washeluting with ethyl acetate/hexane (1:3)

Sources & evidence

ORD record
ord-aa4577bdaef247e182c38c2613b0db87
Source dataset
uspto-grants-2010_08
Patent number
US07786132B2

Reaction notes

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