Phenylacetonitrile → 3-(2-Methyl-pyridin-4-yl)-3-oxo-2-phenyl-propionitrile

HRID 333760Notes

Reaction equation

HRID 333760 reaction equation
CCC([O-])(C)C.[K+].[C:8]1([CH2:14][C:15]#[N:16])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C([O:19][C:20](=O)[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([CH3:27])[CH:22]=1)C>C1COCC1>[CH3:27][C:23]1[CH:22]=[C:21]([C:20](=[O:19])[CH:14]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:15]#[N:16])[CH:26]=[CH:25][N:24]=1

Participants

5

Reactant 3

HCID 8794PhenylacetonitrileHCID 12243767Ethyl 2-methylisonicotinateHCID 23683543Potassium t-amylate

Product 1

HCID 574213293-(2-Methyl-pyridin-4-yl)-3-oxo-2-phenyl-propionitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Potassium tert-pentylate (25% in toluene, 11.3 mL, 20 mmol) was added dropwise to a solution of phenylacteonitrile (590 mg, 5.0 mmol, [CAS Reg. No. 140-29-4]) in THF (8 mL). After 45 min, 2-methyl-isonicotinic acid ethyl ester (998 mg, 6.0 mmol, [CAS Reg. No. 25635-17-0]) was added drop wise, and the mixture was stirred for 3 h at r.t. The solvent was evaporated, and the residue was taken up in ethyl acetate, and washed with 1N aqueous HCl. The combined water layers were saturated with NaCl, and the crude title compound (as an orange precipitate) was collected by filtration. Evaporation of the organic layer gave an additional small crop of crude product. The combined material (1.02 g, 85%) was used in the next step without further purification. 1H NMR (300 MHz, DMSO-D6) 8.81 (1H, d), 7.94 (1H, s), 7.86 (1H, d), 7.78 (2H, d), 7.44 (2H, dd), 7.33 (1H, d), 2.71 (3H, s); MS (m/e)=237.1 [MH+].

Workup

  1. addition25635-17-0]) was added drop wise
  2. customThe solvent was evaporated
  3. washwashed with 1N aqueous HCl
  4. filtrationthe crude title compound (as an orange precipitate) was collected by filtration
  5. customEvaporation of the organic layer
  6. customgave an additional small crop of crude product
  7. customThe combined material (1.02 g, 85%) was used in the next step without further purification

Sources & evidence

ORD record
ord-879ccee1b6e0425399c78d1bfb7fba48
Source dataset
uspto-grants-2014_11
Patent number
US08883786B2

Reaction notes

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