Acetonitrile → Diethyl 4-cyano-4-(6-methoxypyridin-3-yl)heptanedioate

HRID 408629Notes

Reaction equation

HRID 408629 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][C:10]#[N:11])=[CH:5][CH:4]=1.[C:12](#N)[CH3:13].[C:15]([O:19][CH2:20][CH3:21])(=[O:18])[CH:16]=[CH2:17].[Cl-].[NH4+]>CO>[C:10]([C:9]([C:6]1[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)([CH2:17][CH2:16][C:15]([O:19][CH2:12][CH3:13])=[O:18])[CH2:17][CH2:16][C:15]([O:19][CH2:20][CH3:21])=[O:18])#[N:11]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 8821Ethyl AcrylateHCID 25517Ammonium ChlorideHCID 45079846(6-Methoxypyridin-3-yl)acetonitrile

Product 1

HCID 67493723Diethyl 4-cyano-4-(6-methoxypyridin-3-yl)heptanedioate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2.775 g (18.73 mmol) of (6-methoxypyridin-3-yl)acetonitrile (WO2004/111031) are introduced into 125 ml of anhydrous acetonitrile in a 250 ml round-bottomed flask under an argon atmosphere. 0.87 ml (1.87 mmol) of Triton B (40% in methanol) is added, the reaction mixture is brought to reflux and 20.40 ml (187.30 mmol) of ethyl acrylate are added dropwise. The reaction medium is subsequently stirred at reflux for 48 hours, cooled to ambient temperature and concentrated under reduced pressure. The residue thus obtained is poured into a saturated aqueous ammonium chloride solution and extracted twice with dichloromethane. The organic phases are combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue obtained is purified by chromatography on a column of silica gel, elution being carried out with a mixture of chloroform, methanol and aqueous ammonia in the proportions 90/10/1.

Workup

  1. temperatureto reflux
  2. temperatureat reflux for 48 hours
  3. concentrationconcentrated under reduced pressure
  4. customThe residue thus obtained
  5. extractionextracted twice with dichloromethane
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue obtained
  10. customis purified by chromatography on a column of silica gel, elution
  11. additionbeing carried out with a mixture of chloroform, methanol and aqueous ammonia in the proportions 90/10/1

Sources & evidence

ORD record
ord-b51a53e30bfb4521b7d12e6533c04022
Source dataset
uspto-grants-2014_06
Patent number
US08759343B2

Reaction notes

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