Acrylamide → 6-Benzyl-1,2,3,4,5,6,7,8-octahydro-1,6-naphthyridin-2-one

HRID 480569Notes

Reaction equation

HRID 480569 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1CCCC1.[C:20]([NH2:24])(=[O:23])[CH:21]=[CH2:22]>C1(C)C=CC=CC=1.O1CCOCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2[NH:24][C:20](=[O:23])[CH2:21][CH2:22][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6579AcrylamideHCID 192201-Benzyl-4-piperidoneHCID 31268Pyrrolidine

Product 1

HCID 162289266-Benzyl-1,2,3,4,5,6,7,8-octahydro-1,6-naphthyridin-2-oneYield 65%

Reagents, catalysts & solvents 3

HCID 6101p-Toluenesulfonic acidCatalyst2×HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 1-benzyl-4-piperidone (213 g, 1.13 mol) in toluene (700 ml) was added pyrrolidine (190 ml, 2.25 mol), the reaction mixture was fitted with a Dean-Stark head and heated to 150° C. for 18 h. The reaction mixture was cooled and evaporated under reduced pressure, p-toluenesulphonic acid (4.0 g, 0.022 mol) was then added to the residue followed by acrylamide (160 g, 2.25 mol). The reaction mixture was heated with rapid stirring to 90° C. for 1.5 h and then for a further 2 h at 120° C. The cooled mixture was then filtered and the solid obtained washed with acetone followed by ether. The mother liquors were combined, evaporated under reduced pressure and the residue partitioned between EtOAc and H2O. The organic layer was separated, dried over MgSO4 and evaporated under reduced pressure to afford a further batch of solid. The solids were combined and heated to reflux with 4-toluenesulphonic acid (10 g, 0.056 mol) in dioxane (400 ml) for 18 h. On cooling, a colourless crystalline product was formed which was filtered and washed with EtOAc to afford the subtitle compound as colourless crystals (176 g, 65%). Rf 0.1 (EtOAc). 1H NMR (CDCl3) δ: 2.20 (4H, d), 2.50 (2H, t), 2.70 (2H, s), 3.00 (2H,s), 3.65 (2H, s), 7.20-7.45 (5H, m).

Workup

  1. customthe reaction mixture was fitted with a Dean-Stark head
  2. temperatureThe reaction mixture was cooled
  3. additionwas then added to the residue
  4. temperatureThe reaction mixture was heated
  5. waitfor a further 2 h at 120° C
  6. filtrationThe cooled mixture was then filtered
  7. customthe solid obtained
  8. washwashed with acetone
  9. customevaporated under reduced pressure
  10. customthe residue partitioned between EtOAc and H2O
  11. customThe organic layer was separated
  12. dry with materialdried over MgSO4
  13. customevaporated under reduced pressure
  14. customto afford a further batch of solid
  15. temperatureheated
  16. temperatureOn cooling
  17. customa colourless crystalline product was formed which
  18. filtrationwas filtered
  19. washwashed with EtOAc

Sources & evidence

ORD record
ord-2264930d13b346058c4f30dc23fdd5bf
Source dataset
uspto-grants-2003_11
Patent number
US06653302B2

Reaction notes

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