Diethyl (cyanomethyl)phosphonate → (2E)-3-(5-morpholin-4-ylpyridin-3-yl)acrylonitrile

HRID 1501459Notes

Reaction equation

HRID 1501459 reaction equation
[C:1]([CH2:3]P(=O)(OCC)OCC)#[N:2].CC(C)([O-])C.[K+].[N:18]1([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([CH:31]=2)[CH:29]=O)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1>C1COCC1>[N:18]1([C:24]2[CH:31]=[C:28](/[CH:29]=[CH:3]/[C:1]#[N:2])[CH:27]=[N:26][CH:25]=2)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 574778965-Morpholinonicotinaldehyde

Product 1

HCID 66597176(2E)-3-(5-morpholin-4-ylpyridin-3-yl)acrylonitrileYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of diethyl cyanomethylphosphonate (70 mg, 0.0004 mol) in THF (2 mL, 0.02 mol) cooled at 0° C. was added 1.0 M potassium tert-butoxide in THF (0.50 mL) dropwise. The cold bath was removed and the reaction was warmed to room temperature over 30 minutes. The reaction was cooled to 0° C. and a solution of 5-morpholin-4-ylnicotinaldehyde (70 mg, 0.0004 mol) in THF (2 mL, 0.02 mol) was added dropwise. The reaction was stirred at room temperature for 4 h, quenched with water and extracted with ethyl acetate. The combined organic layers were washed with saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated to give (2E)-3-(5-morpholin-4-ylpyridin-3-yl)acrylonitrile (75 mg, 100%) as a mixture of isomers; LC/MS: 216 (M+1).

Workup

  1. customThe cold bath was removed
  2. temperatureThe reaction was cooled to 0° C.
  3. customquenched with water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic layers were washed with saturated sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-cbd28cac29244866b22a89c4e648bda9
Source dataset
uspto-grants-2015_12
Patent number
US09206187B2

Reaction notes

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