2-Fluoro-5-formylbenzonitrile → 4-(3-Cyano-4-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile

HRID 1038380Notes

Reaction equation

HRID 1038380 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7]([CH:10]=O)=[CH:6][C:3]=1[C:4]#[N:5].[NH2:12]/[C:13](/[CH3:17])=[CH:14]\[C:15]#[N:16]>C(O)(=O)C>[C:4]([C:3]1[CH:6]=[C:7]([CH:10]2[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[NH:12][C:2]([CH3:9])=[C:3]2[C:4]#[N:5])[CH:8]=[CH:9][C:2]=1[F:1])#[N:5]

Participants

4

Reactant 2

HCID 27695822-Fluoro-5-formylbenzonitrileHCID 5325263(2Z)-3-Amino-2-butenenitrile

Product 1

HCID 597632464-(3-Cyano-4-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrileYield 160.7%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

30 g (201.2 mmol) 2-fluoro-5-formylbenzonitrile and 35 g (431.6 mmol) 3-aminocrotononitrile were dissolved in acetic acid (500 ml) and heated to 90° C. After 4 h, the reaction mixture was cooled to rt, concentrated, neutralized with a saturated aqueous solution of sodium bicarbonate, and extracted with ethyl acetate. The organic extracts were combined, dried over sodium sulfate and concentrated under reduced pressure. The remaining solid was dissolved in ethyl acetate, and hexane was added. The precipitate was filtered off to afford the title compound (45 g, 80% of th.) as a pale yellow solid.

Workup

  1. temperaturethe reaction mixture was cooled to rt
  2. concentrationconcentrated
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe remaining solid was dissolved in ethyl acetate
  7. additionhexane was added
  8. filtrationThe precipitate was filtered off

Sources & evidence

ORD record
ord-5d1dad6b490b4d95877c85768ddceb25
Source dataset
uspto-grants-2013_10
Patent number
US08551989B2

Reaction notes

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