Sodium Cyanide → 2-(quinolin-2-yl)acetonitrile

HRID 2416367Notes

Reaction equation

HRID 2416367 reaction equation
Cl[CH2:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.[C-:13]#[N:14].[Na+]>C(O)C.O.CCCCCCC.C(OCC)(=O)C.C1COCC1>[N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[CH:12][C:3]=1[CH2:2][C:13]#[N:14]

Participants

8

Reactant 2

HCID 8929Sodium CyanideHCID 203942-(Chloromethyl)quinoline

Product 1

HCID 2643022-(quinolin-2-yl)acetonitrileYield 74.5%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

To a solution of 2-(chloromethyl)quinoline (20.74 g, 117 mmol) in ethanol and water (200 mL, 4:1 ratio) was added NaCN (5.73 g, 117 mmol), and the reaction mixture was heated at reflux for 18 h. The reaction mixture was cooled to ambient temperature; diluted with a mixture of heptane, ethyl acetate, and THF; and washed with a 5% aqueous solution of K2CO3 and brine. The organic layer was isolated and dried over MgSO4. Purification by column chromatography with an elution gradient of 75:25 heptane/ethyl acetate to 65:35 heptane/ethyl acetate afforded 14.6 g (74.5%) of desired product. Results of 1H NMR spectroscopy and electrospray mass spectroscopy are consistent with the product. 1H NMR (300 MHz, CDCl3): δ 4.12 (s, 2H), 7.66 (m, 2H), 7.76 (m, 2H), 7.84 (d, J=8.2 Hz, 1H), 8.06 (d, J=8.2 Hz, 1H), 8.22 (d, J 8.5 Hz, 1H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 18 h
  3. washand washed with a 5% aqueous solution of K2CO3 and brine
  4. customThe organic layer was isolated
  5. dry with materialdried over MgSO4
  6. customPurification by column chromatography with an elution gradient of 75:25 heptane/ethyl acetate to 65:35 heptane/ethyl acetate

Sources & evidence

ORD record
ord-8884c602cb8149e7825de48fa98ed043
Source dataset
uspto-grants-2004_11
Patent number
US06824893B2

Reaction notes

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