Sodium Hydroxide → 1-[(4-Methoxyphenyl)methyl]-3-methylidenepiperidin-2-one

HRID 262789Notes

Reaction equation

HRID 262789 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:20]=[CH:19][C:7]([CH2:8][N:9]2[CH2:18][CH2:17][CH2:16][CH:11]([C:12](OC)=O)[CH2:10]2)=[CH:6][CH:5]=1.[OH-:21].[Na+]>CO.O>[CH3:2][O:3][C:4]1[CH:20]=[CH:19][C:7]([CH2:8][N:9]2[CH2:18][CH2:17][CH2:16][C:11](=[CH2:12])[C:10]2=[O:21])=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 14181476methyl N-(p-methoxybenzyl)nipecotate hydrochloride

Product 1

HCID 127744231-[(4-Methoxyphenyl)methyl]-3-methylidenepiperidin-2-oneYield 71.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of methyl N-(p-methoxybenzyl)nipecotate hydrochloride (30.7 g) and 8.4 g of sodium hydroxide in 900 ml of methanol and 45 ml of water is stirred at room temperature for seventeen hours. The solution is evaporated to dryness in vacuo, the residue diluted with toluene, and this again evaporated to dryness in vacuo. To the residue is added 1 liter of acetic anhydride and 140 ml of triethylamine, and the resulting mixture is heated under reflux for four hours. The reaction mixture is evaporated to dryness in vacuo, the residue taken up in chloroform, washed with water, dried, and concentrated in vacuo. The residual oil is chromatographed on silica gel using 1:1 hexane-ethyl acetate as the eluant, and yields 16.9 g of 1-(p-methoxybenzyl)-3-methylene-2-piperidone as a chromatographically pure yellow oil. Alternatively, the oil can be distilled to give analytically pure 1-(p-methoxybenzyl)-3-methylene-2-piperidone, b.p. 145°-155°/0.05 mm.

Workup

  1. customThe solution is evaporated to dryness in vacuo
  2. additionthe residue diluted with toluene
  3. customthis again evaporated to dryness in vacuo
  4. additionTo the residue is added 1 liter of acetic anhydride and 140 ml of triethylamine
  5. temperaturethe resulting mixture is heated
  6. temperatureunder reflux for four hours
  7. customThe reaction mixture is evaporated to dryness in vacuo
  8. washwashed with water
  9. customdried
  10. concentrationconcentrated in vacuo
  11. customThe residual oil is chromatographed on silica gel using 1:1 hexane-ethyl acetate as the eluant

Sources & evidence

ORD record
ord-de6acd2070b543049b7ab878e9cfe243
Source dataset
uspto-grants-1979_05
Patent number
US04154946

Reaction notes

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