Acrylonitrile → (S)-3-[[(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-3-yl)methyl](phenylmethyl)amino]-propanenitrile

HRID 1793340Notes

Reaction equation

HRID 1793340 reaction equation
[C:1]1([CH2:7][NH:8][CH2:9][C@@H:10]2[O:19][C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[O:12][CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:20](#[N:23])[CH:21]=[CH2:22]>C(O)C>[O:12]1[C:13]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[O:19][C@@H:10]([CH2:9][N:8]([CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:22][CH2:21][C:20]#[N:23])[CH2:11]1

Participants

4

Reactant 2

HCID 7855Acrylonitrile4×HCID 69256693HCID 69256693, compound

Product 1

HCID 69256506(S)-3-[[(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-3-yl)methyl](phenylmethyl)amino]-propanenitrileYield 99.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Intermediate (55) (0.0195 mol) was dissolved in ethanol (50 ml). 2-Propenenitrile (0.02 mol) was added and the reaction mixture was stirred and refluxed overnight. Additional 2-propenenitrile (0.02 mol) was added and the reaction mixture was stirred and refluxed for 2 hours. Additional 2-propenenitrile (0.02 mol) was added and the reaction mixture was stirred and refluxed for 6 hours. Additional 2-propenenitrile (0.02 mol) was added and the reaction mixture was stirred and refluxed overnight. The solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 97/3). The product fractions were collected and the solvent was evaporated, yielding 6.0 g of (S)-3-[[(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-3-yl)methyl](phenylmethyl)amino]-propanenitrile (intermediate 56).

Workup

  1. temperaturerefluxed overnight
  2. stirringthe reaction mixture was stirred
  3. temperaturerefluxed for 2 hours
  4. stirringthe reaction mixture was stirred
  5. temperaturerefluxed for 6 hours
  6. stirringthe reaction mixture was stirred
  7. temperaturerefluxed overnight
  8. customThe solvent was evaporated
  9. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 97/3)
  10. customThe product fractions were collected
  11. customthe solvent was evaporated

Sources & evidence

ORD record
ord-38297af7c6ec49538e0643e0ab7da876
Source dataset
uspto-grants-2006_07
Patent number
US07081453B2

Reaction notes

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