Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl ester → tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate

HRID 495777Notes

Reaction equation

HRID 495777 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]([CH:20]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:17][CH2:18][CH3:19])=[O:16]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[CH:20][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 70670Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl esterHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 10333298tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylateYield 88.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

4-Oxopiperidine-1-carboxylic acid tert-butyl ester (8.0 g; 40.2 mmol) was dissolved in toluene (80 mL). Carboethoxymethylene triphenylphosphorane (17.5 g; 50.2 mmol) was added and the reaction mixture was heated 12 hours at reflux. The reaction mixture was evaporated in vacuo and the residue was chromatographed on silica (4.5×30 cm) using diethyl ether/heptane (1:1) as eluent to afford 9.5 g (35.7 mmol) of 4-Ethoxycarbonylmethylenepiperidine-1-carboxylic acid tert-butyl ester, which was dissolved in 1,4-dioxane and cooled to 0° C. Lithium hydroxide (2.73 g; 114 mmol) was dissolved in water (20 mL) and added. The reaction mixture was stirred for 12 hours at room temperature. Ethyl acetate (200 mL) and water (100 mL) was added. Sodium hydrogen sulfate (10%; aqueous solution) was added to pH 2. The organic phase was washed with water (100 mL), dried (magnesium sulfate) and evaporated in vacuo to afford 5.49 g of 4-carboxymethylenepiperidine-1-carboxylic acid tert-butyl ester.

Workup

  1. temperaturethe reaction mixture was heated 12 hours
  2. temperatureat reflux
  3. customThe reaction mixture was evaporated in vacuo
  4. customthe residue was chromatographed on silica (4.5×30 cm)

Sources & evidence

ORD record
ord-b4e05f596c24433589115272e57c819c
Source dataset
uspto-grants-2005_09
Patent number
US06939880B2

Reaction notes

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