Hydrochloric Acid → 1-Benzyl-4-(4-methoxyphenyl)-1,2,3,6-tetrahydropyridine

HRID 1411400Notes

Reaction equation

HRID 1411400 reaction equation
Cl.[CH2:2]([N:9]1[CH2:14][CH2:13][C:12]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)(O)[CH2:11][CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[OH-].[Na+]>O1CCOCC1>[CH2:2]([N:9]1[CH2:10][CH:11]=[C:12]([C:16]2[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=2)[CH2:13][CH2:14]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 159073291-Benzyl-4-(4-methoxyphenyl)piperidin-4-ol

Product 1

HCID 106364031-Benzyl-4-(4-methoxyphenyl)-1,2,3,6-tetrahydropyridineYield 53.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

6 M HCl (100 mL, aqueous) was added to a solution of 1-benzyl-4-(4-methoxyphenyl)piperidin-4-ol (12.31 g, 41.36 mmol) in dioxane (50 mL), and the reaction was heated to strong reflux (110° C.). After 2 hours, the reaction was not complete. The heat was turned off and the reaction was left to stir at ambient temperature for 2 days. The reaction had progressed but was not complete so it was heated to 110° C. After 1 hour, the reaction was cooled and the volume was reduced by approximately one third. The solution was then cooled in an ice bath and neutralized with NaOH pellets. The thick suspension was filtered. The precipitate was rinsed with water and then dried under vacuum at 70° C. to afford 6.2 g (47%) of the titled compound. 1H NMR (400 MHz, CDCl3) δ ppm 2.74-2.62 (m, 1H), 3.30-3.06 (m, 2H), 3.50 (d, J=18.5, 1H), 3.67-3.56 (m, 1H), 3.82 (s, 3H), 4.03-3.90 (m, 1H), 4.21 (dd, J=5.7, 13.0, 1H), 4.34 (dd, J=5.1, 13.0, 1H), 5.88 (s, 1H), 6.88 (d, J=8.7, 2H), 7.32 (d, J=8.7, 2H), 7.51-7.43 (m, 3H), 7.71 (dd, J=2.7, 6.3, 2H), 12.85 (s, 1H); MS (ESI) m/z 280 (M+H)+; MS (DCI) m/z 280 (M+H)+.

Workup

  1. temperaturethe reaction was heated
  2. waitthe reaction was left
  3. temperaturewas heated to 110° C
  4. waitAfter 1 hour
  5. temperaturethe reaction was cooled
  6. temperatureThe solution was then cooled in an ice bath
  7. filtrationThe thick suspension was filtered
  8. washThe precipitate was rinsed with water
  9. customdried under vacuum at 70° C.

Sources & evidence

ORD record
ord-cff3286e35854327b4b79c608b779d81
Source dataset
uspto-grants-2014_12
Patent number
US08921514B2

Reaction notes

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