Hydrochloric Acid → 2-[4-(3,5-Dimethyl-pyridin-4-yl)-3,5-dimethyl-phenyl]-malononitrile

HRID 1801424Notes

Reaction equation

HRID 1801424 reaction equation
[H-].[Na+].[C:3](#[N:7])[CH2:4][C:5]#[N:6].I[C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([C:16]2[C:21]([CH3:22])=[CH:20][N:19]=[CH:18][C:17]=2[CH3:23])=[C:11]([CH3:24])[CH:10]=1.Cl>COCCOC>[CH3:22][C:21]1[CH:20]=[N:19][CH:18]=[C:17]([CH3:23])[C:16]=1[C:12]1[C:11]([CH3:24])=[CH:10][C:9]([CH:4]([C:3]#[N:7])[C:5]#[N:6])=[CH:14][C:13]=1[CH3:15]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8010MalononitrileHCID 24758Sodium hydrideHCID 58510520HCID 58510520, compound

Product 1

HCID 585105262-[4-(3,5-Dimethyl-pyridin-4-yl)-3,5-dimethyl-phenyl]-malononitrileYield 95.5%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To an ice-cooled suspension of NaH (0.12 g, 5.0 mmol) in anhydrous 1,2-dimethoxyethane (8 mL) was added dropwise via syringe a solution of malononitrile (0.165 g, 2.50 mmol) in anhydrous 1,2-dimethoxyethane (2 mL) under N2. The mixture was stirred for 1 h at room temperature under N2. Next, 11 (0.674 g, 2.00 mmol) and tetrakis(triphenyphosphine)palladium(0) (0.232 g, 0.200 mmol) were added to the resulting pink suspension under an N2 flow. The reaction mixture was next stirred at 85° C. under N2 for 5 h. The solvent was then removed under reduced pressure. The resulting solid was washed with benzene (20 mL), dissolved in water, and filtered to give a dark-yellow aqueous solution. This solution was neutralized with 5% HCl to pH=7, and the resulting yellow precipitate was collected by filtration to give an orange solid. The crude product was purified by flash chromatography on silica gel eluting with 1:1 hexane:ethyl acetate, to give 0.525 g (95.5%) of the title compound as red solid: mp 58-60° C.; 1H NMR (400 MHz, CDCl3): δ 8.412 (s, 2H), 7.286 (s, 2H), 5.100 (s, 1H), 1.946 (s, 6H), 1.895 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 149.066, 146.564, 139.513, 137.283, 130.441, 126.692, 125.518, 112.024, 28.059, 19.988, 16.704; Anal. Calcd. for C18H17N3.H2O: C, 73.69; H, 6.53; N, 14.32. Found; C, 73.36; H, 6.35; N, 14.07.

Workup

  1. stirringThe reaction mixture was next stirred at 85° C. under N2 for 5 h
  2. customThe solvent was then removed under reduced pressure
  3. washThe resulting solid was washed with benzene (20 mL)
  4. dissolutiondissolved in water
  5. filtrationfiltered
  6. customto give a dark-yellow aqueous solution
  7. filtrationthe resulting yellow precipitate was collected by filtration
  8. customto give an orange solid
  9. customThe crude product was purified by flash chromatography on silica gel eluting with 1:1 hexane

Sources & evidence

ORD record
ord-8cd88511f50342b687ab71902e9c9fd1
Source dataset
uspto-grants-2013_01
Patent number
US08349222B2

Reaction notes

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