Ethanol → Ethyl [1-acetyl-3-(4-methylbenzyl)piperidin-3-yl]acetate

HRID 1860646Notes

Reaction equation

HRID 1860646 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH2:7][C:6]([CH2:18][CH:19]=[O:20])([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[CH2:5]1)(=[O:3])[CH3:2].[OH-].[Na+].[CH2:23]([OH:25])[CH3:24]>O.[N+]([O-])([O-])=O.[Ag+]>[C:1]([N:4]1[CH2:9][CH2:8][CH2:7][C:6]([CH2:18][C:19]([O:25][CH2:23][CH3:24])=[O:20])([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=2)[CH2:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 86591292[1-Acetyl-3-(4-methylbenzyl)piperidin-3-yl]acetaldehyde

Product 1

HCID 86591291Ethyl [1-acetyl-3-(4-methylbenzyl)piperidin-3-yl]acetate

Reagents, catalysts & solvents 2

HCID 24470Silver NitrateCatalyst2×HCID 962WaterSolvent3×

Conditions

Temperature
25 °C

Procedure

Silver nitrate (1.87 g, 11.0 mmol) was dissolved in 3 ml H2O. It was added to a solution of the product from STEP 6 (1.6 g, 5.5 mmol) in 25 ml ethanol. A solution prepared from dissolving NaOH (0.88 g, 22.0 mmol) in 4.0 ml H2O was added dropwise to the silver nitrate solution. The reaction was stirred at 25° C. for 2 h. The reaction was diluted with 15 ml H2O. The ethanol was removed and the resulting residue was extracted with ethyl acetate (2×60 ml). The aqueous extracts were acidified with 1 N aqueous HCl solution to PH=5, and extracted with ethyl acetate (3×100 ml). The organic layer was washed with 15 ml brine, dried with MgSO4, filtered and concentrated to afford a 1.1 g of clean oil. The oil was dissolved in 30 ml ethanol and 15 ml 2M HCl/dioxane. The reaction was stirred at room temperature for 18 h and concentrated. The residue was purified by chromatography (on silica gel, CH2Cl2/MeOH/NH4OH=95/5/0.1) to give 0.88 g of a gummy solid. The 1H NMR spectrum of the product was consistent for the proposed structure.

Workup

  1. customA solution prepared
  2. customThe ethanol was removed
  3. extractionthe resulting residue was extracted with ethyl acetate (2×60 ml)
  4. extractionextracted with ethyl acetate (3×100 ml)
  5. washThe organic layer was washed with 15 ml brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-4f89af2ba2914153a6b572264067582f
Source dataset
uspto-grants-2003_03
Patent number
US06531494B1

Reaction notes

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