Hydrochloric Acid → 4-Benzyloxybenzoylmalononitrile

HRID 1518285Notes

Reaction equation

HRID 1518285 reaction equation
[H-].[Na+].[C:3](#[N:7])[CH2:4][C:5]#[N:6].[CH2:8]([O:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][CH:17]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl>C1COCC1>[CH2:8]([O:15][C:16]1[CH:17]=[CH:18][C:19]([C:20]([CH:4]([C:3]#[N:7])[C:5]#[N:6])=[O:21])=[CH:23][CH:24]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8010MalononitrileHCID 24758Sodium hydrideHCID 37664104-Benzyloxybenzoylchloride

Product 1

HCID 221697854-BenzyloxybenzoylmalononitrileYield 64.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

NaH (1.657 g, 60%, 41.4 mmol) was suspended in THF (10 mL). To this suspension was added malononitrile (1.368 g, 20.71 mmol) in THF (10 mL) at 0° C. dropwise over 10 minutes. The suspension was stirred for additional 20 minutes. To this solution was added compound 31A (5.11 g, 20.71 mmol) in THF (40 mL) portion wise. Afterwards, the solution was warmed to rt and stirred for 30 minutes. The pH of the solvent was adjusted to 1 with concentrated HCl. The reaction mixture was concentrated, and partitioned between water and EtOAc. The aqueous layer was extracted with additional EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was triturated with 1:1 Hex/EtOAc (50 mL) to give a solid which was collected by filtration to provide 3.7 g of the desired product 31B: 1H NMR (DMSO-d6): δ 7.60-7.63 (m, 2H), 7.32-7.47 (m, 5H), 7.03-7.07 (m, 2H), 5.16 (s, 2H). MS (DCI(+)): m/z 294 (M+NH4).

Workup

  1. stirringstirred for 30 minutes
  2. concentrationThe reaction mixture was concentrated
  3. custompartitioned between water and EtOAc
  4. extractionThe aqueous layer was extracted with additional EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was triturated with 1:1 Hex/EtOAc (50 mL)
  10. customto give a solid which
  11. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-afda21e6fead4a3187b19ff45c4c6ff0
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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