2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → HCID 86707847, compound

HRID 535759Notes

Reaction equation

HRID 535759 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:16]2[CH2:19][CH2:18][CH2:17]2)[N:5]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1Br.[Li]CCCC.[Cl:25][C:26]1[N:31]=[CH:30][CH:29]=[CH:28][N:27]=1.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N.[OH-].[Na+]>C1COCC1.O.C1COCC1>[Br:1][C:2]1[N:3]=[C:4]([CH:16]2[CH2:19][CH2:18][CH2:17]2)[N:5]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[C:28]1[CH:29]=[CH:30][N:31]=[C:26]([Cl:25])[N:27]=1

Participants

8

Reactant 5

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 14798Sodium HydroxideHCID 744042-ChloropyrimidineHCID 67053515HCID 67053515, compoundHCID 178418339Butyllithium

Product 1

HCID 86707847HCID 86707847, compoundYield 101.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4,5-dibromo-2-cyclobutyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (0.43 g, 1.0 mmol) in THF (5 mL) at −78° C. under nitrogen was added n-BuLi (2.0 M in pentane, 0.68 mL, 1.36 mmol), dropwise over 5 minutes. After 40 minutes, a solution of 2-chloropyrimidine (0.17 g, 1.47 mmol) in THF (5 mL) was added dropwise over one minute. The reaction was stirred at −78° C. for 1 hour and LCMS indicated complete reaction. The reaction was slowly quenched with 1:1 water-THF solution (50 mL) from an addition funnel, keeping the temperature between −40° C. and −35° C. After 15 minutes of stirring, a solution of DDQ (0.36 g, 1.61 mmol) in THF (20 mL) was added slowly, and the mixture was stirred for 15 minutes under ice water cooling. Aqueous 2.0 N NaOH solution (12 mL) was then added followed by 1:1 water-THF solution (12 mL). The resulting mixture was partitioned with EtOAc and the layers separated. The organic layer was washed with water (2×), brine (2×), dried (Na2SO4), and concentrated to give a brown oil (0.45 g) as 4-(4-bromo-2-cyclobutyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine which was carried forward without further purification: LCMS (m/z) 443.1 (MH+), tR=1.27 minutes.

Workup

  1. waitAfter 40 minutes
  2. customreaction
  3. customThe reaction was slowly quenched with 1:1 water-THF solution (50 mL) from an addition funnel
  4. customthe temperature between −40° C. and −35° C
  5. stirringAfter 15 minutes of stirring
  6. stirringthe mixture was stirred for 15 minutes under ice water cooling
  7. customThe resulting mixture was partitioned with EtOAc
  8. customthe layers separated
  9. washThe organic layer was washed with water (2×), brine (2×)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-1c8f292e73ca44df96d145465581344b
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

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