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

HRID 1695539Notes

Reaction equation

HRID 1695539 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1.[Cl:13][C:14]1[N:19]=[CH:18][CH:17]=[CH:16][N:15]=1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.[OH-].[Na+]>CCOCC.C1COCC1.O.CCCCCC>[Cl:13][C:14]1[N:19]=[C:18]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[CH:17]=[CH:16][N:15]=1

Participants

10

Reactant 5

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 122863-BromopyridineHCID 14798Sodium HydroxideHCID 744042-ChloropyrimidineHCID 178418339Butyllithium

Product 1

HCID 118055432-Chloro-4-(pyridin-3-yl)pyrimidine

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-75 °C

Procedure

To a solution of butyllithium (1.6M in hexanes, 9.7 ml, 16 mmol) in 25 ml of anhydrous ether at −78° C. was added 3-bromopyridine (1.5 ml, 16 mmol) over 5 min. The resulting mixture was stirred at −75° C. for 1 h. A suspension of 2-chloropyrimidine (1.8 g, 16 mmol) in 15 ml of ether was then added in portions over 8 min. The resulting suspension was stirred for 30 min at −30° C. and allowed to warm to 0° C. for 1 h. The reaction was quenched with water (0.5 ml, 1.5 eq.) in THF (5 ml) and then 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (3.8 g, 17 mmol) in THF (12 ml) was added. The resulting suspension was stirred at RT for 15 min, then cooled to 0° C. Hexane (13 mL) was added followed by 0° C. solution of NaOH (12 ml, 3N). The suspension was stirred at 0° C. for 5 min, 50 ml of water was added and the layers were separated. The organic layer was dried (Na2SO4) and concentrated in vacuo. The crude product was dissolved in DCM and chromatographed through a Redi-Sep® pre-packed silica gel column (120 g), eluting with a gradient of 20% to 65% EtOAc in hexane, to provide 2-chloro-4-(pyridin-3-yl)pyrimidine as off-white solid. Found M+H+=192, 194

Workup

  1. additionwas then added in portions over 8 min
  2. stirringThe resulting suspension was stirred for 30 min at −30° C.
  3. temperatureto warm to 0° C. for 1 h
  4. stirringThe resulting suspension was stirred at RT for 15 min
  5. temperaturecooled to 0° C
  6. customfollowed by 0° C.
  7. stirringThe suspension was stirred at 0° C. for 5 min
  8. customthe layers were separated
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. dissolutionThe crude product was dissolved in DCM
  12. customchromatographed through a Redi-Sep® pre-packed silica gel column (120 g)
  13. washeluting with a gradient of 20% to 65% EtOAc in hexane

Sources & evidence

ORD record
ord-90f8a08f02eb4178a2adf4e92f85c1b5
Source dataset
uspto-grants-2012_04
Patent number
US08163742B2

Reaction notes

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