Sodium ethoxide → 1-[2-(Chroman-3-yl)ethyl]-piperidine-4-carboxylic acid ethyl ester

HRID 1032423Notes

Reaction equation

HRID 1032423 reaction equation
[CH2:1]([O:3][C:4]([CH2:6][CH2:7][CH2:8][N:9]([CH2:22][CH2:23]Br)[CH2:10][CH2:11][CH:12]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[O:14][CH2:13]1)=[O:5])[CH3:2].[O-]CC.[Na+]>CN(C)C=O>[CH2:1]([O:3][C:4]([CH:6]1[CH2:23][CH2:22][N:9]([CH2:10][CH2:11][CH:12]2[CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[O:14][CH2:13]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 2723922Sodium ethoxideHCID 14838456N-(3-ethoxycarbonylpropyl)-N-(2-bromoethyl)-N-[2-(chroman-3-yl)ethyl]amine

Product 1

HCID 148384361-[2-(Chroman-3-yl)ethyl]-piperidine-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

At room temperature and while stirring, a solution of 11.94 g (30 mmol) of N-(3-ethoxycarbonylpropyl)-N-(2-bromoethyl)-N-[2-(chroman-3-yl)ethyl]amine in 40 ml of absolute dimethylformamide is added dropwise within a period of 20 minutes to a suspension of 2.72 g (40 mmol) of sodium ethoxide in 30 ml of dimethylformamide. The reaction mixture is stirred for 16 hours at room temperature and then concentrated to dryness by evaporation under a high vacuum. Diethyl ether is added to the residue and extraction is carried out with cold 2N hydrochloric acid. The combined hydrochloric acid extracts are extracted by shaking with dichloromethane and the dichloromethane phases are dried over sodium sulphate and concentrated by evaporation in vacuo. The crude product is obtained as the residue and is chromatographed on 500 g of silica gel (0.040-0.063 mm) using ethyl acetate as the eluant. The eluate is concentrated by evaporation to yield 1-[2-(chroman-3-yl)ethyl]-piperidine-4-carboxylic acid ethyl ester in the form of a colourless oil. The 1-[2-(chroman-3-yl)ethyl]-piperidine-4-carboxylic acid ethyl ester hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from ethanol/diethyl ether and melts at 182°-186°.

Workup

  1. stirringThe reaction mixture is stirred for 16 hours at room temperature
  2. concentrationconcentrated to dryness by evaporation under a high vacuum
  3. additionDiethyl ether is added to the residue and extraction
  4. extractionThe combined hydrochloric acid extracts are extracted
  5. stirringby shaking with dichloromethane
  6. dry with materialthe dichloromethane phases are dried over sodium sulphate
  7. concentrationconcentrated by evaporation in vacuo
  8. customThe crude product is obtained as the residue
  9. customis chromatographed on 500 g of silica gel (0.040-0.063 mm)
  10. concentrationThe eluate is concentrated by evaporation

Sources & evidence

ORD record
ord-914468f7cee14ccf99dfaaf8cd2b9ab6
Source dataset
uspto-grants-1990_09
Patent number
US04957928

Reaction notes

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