Methanol → 4-(3-Methoxyphenyl)-1-methyl-3-methylidenepiperidin-2-one

HRID 1449243Notes

Reaction equation

HRID 1449243 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH:10]2[C:16](OCC)=O)[CH:6]=[CH:7][CH:8]=1.[OH-:21].[Na+].CO>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:14][CH2:13][N:12]([CH3:15])[C:11](=[O:21])[C:10]2=[CH2:16])[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 12947549Ethyl 4-(3-methoxyphenyl)-1-methylpiperidine-3-carboxylate

Product 1

HCID 129475504-(3-Methoxyphenyl)-1-methyl-3-methylidenepiperidin-2-oneYield 93.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The ester ethyl 4-(3'-methoxyphenyl)-1-methylpiperidine-3-carboxylate (23)(5.0 g, 17.5 mmol), NaOH (1.49 g, 35 mmol), CH3OH (50 mL), and H2O (25 mL) were refluxed for 5 h. After the thorough removal of solvents, the residue was mixed with acetic anhydride (50 mL) and refluxed for 1 h, then cooled and evaporated and the crude reaction product partitioned between CHCl3 (50 mL) and saturated NaHCO3 (50 mL, pH 8). The aqueous layer was extracted with CHCl3 (2×50 mL) and the combined organic phases dried and evaporated. Distillation gave 3.77 g (92%) of 4-(3'-methoxyphenyl)-1-methyl-3-methylene-2-piperidone (24). Recrystallization (CH3Cl2 /hexane) gave the analytical sample: mp 67°-70° C: NMR δ 7.29 (m, 1H), 6.82 (m, 3H), 6.40 (t,J=2 Hz, 1H), 5.07 (t,J=2 Hz, 1H), 3.75 (s, 3H), 3.34 (m, 2H), 3.04 (s, 3H), 2.17 (m, 2H); IR (KBr) 1645, 1600 cm-1 ; mass spectrum m/e (real intensity) 231 (100), 216 (13). Anal. Calcd for C14H17NO2 : C, 72.7; H, 7.4; N, 6.1. Found: C, 72.6; H, 7.3; N, 6.0.

Workup

  1. customAfter the thorough removal of solvents
  2. additionthe residue was mixed with acetic anhydride (50 mL)
  3. temperaturerefluxed for 1 h
  4. temperaturecooled
  5. customevaporated
  6. customthe crude reaction product
  7. custompartitioned between CHCl3 (50 mL) and saturated NaHCO3 (50 mL, pH 8)
  8. extractionThe aqueous layer was extracted with CHCl3 (2×50 mL)
  9. customthe combined organic phases dried
  10. customevaporated
  11. distillationDistillation

Sources & evidence

ORD record
ord-c21a0d582b1c471b96fc36f93ffa28af
Source dataset
uspto-grants-1980_02
Patent number
US04189583

Reaction notes

Loading…