Hydrochloric Acid → HCID 86665178, compound

HRID 1912889Notes

Reaction equation

HRID 1912889 reaction equation
[H-].[Na+].[C:3](#[N:7])[CH2:4][C:5]#[N:6].I[C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=1.Cl>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[F:17][C:16]([F:18])([F:19])[O:15][C:12]1[CH:13]=[CH:14][C:9]([CH:4]([C:3]#[N:7])[C:5]#[N:6])=[CH:10][CH:11]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8010MalononitrileHCID 24758Sodium hydrideHCID 27772941-Iodo-4-(trifluoromethoxy)benzene

Product 1

HCID 86665178HCID 86665178, compoundYield 95.9%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (2.87 g, 114 mmol) in THF (15 mL), malononitrile (4.77 mL, 76 mmol) in 2 mL of THF was added dropwise at 0° C. After the gas evolution ceased, 1-iodo-4-(trifluoromethoxy)benzene (5.92 mL, 37.8 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.797 g, 1.135 mmol) were added. This mixture was then heated at reflux under nitrogen overnight. The suspension was cooled to ambient temperature, treated with water, acidified with 1N HCl and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated and purified on silica gel (0˜30% ethyl acetate in hexanes) to give 8.2 g of product as a tan solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.48-7.65 (m, 2H) 7.37 (d, J=8.35 Hz, 2H) 5.09 (s, 1H). MS (ESI) m/z 225.1 (M−H)−.

Workup

  1. additionwas added dropwise at 0° C
  2. temperatureThis mixture was then heated
  3. temperatureat reflux under nitrogen overnight
  4. extractionextracted with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. custompurified on silica gel (0˜30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5b4d2e43cf5d4d9c904ae61d58209792
Source dataset
uspto-grants-2013_12
Patent number
US08609669B2

Reaction notes

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