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

HRID 1032400Notes

Reaction equation

HRID 1032400 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][NH:8][CH2:7]1)=[O:5])[CH3:2].C(N(C(C)C)C(C)C)C.C1(C)C=CC(S(O[CH2:31][CH2:32][CH:33]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[O:35][CH2:34]2)(=O)=O)=CC=1>CN(C)C=O>[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH2:31][CH2:32][CH:33]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[O:35][CH2:34]2)[CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 98969Ethyl nipecotateHCID 148384153-[2-(p-Toluenesulphonyloxy)ethyl]chroman

Product 1

HCID 148384351-[2-(Chroman-3-yl)ethyl]-piperidine-3-carboxylic acid ethyl esterYield 97.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

First 3.76 g (24 mmol) of piperidine-3-carboxylic acid ethyl ester and then 3.1 g (24 mmol) of N-ethyl-N,N-diisopropylamine are added to a solution of 3.98 g (12 mmol) of 3-[2-(p-toluenesulphonyloxy)ethyl]chroman in 50 ml of absolute dimethylformamide. The mixture is stirred for 16 hours at 60° and, after cooling, is concentrated by evaporation under a high vacuum. Water is added to the oily residue and extraction is carried out with diethyl ether. The combined organic phases are extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline, while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulphate and concentrated by evaporation in vacuo. 3.7 g (97.3%) of 1-[2-(chroman-3-yl)ethyl]-piperidine-3-carboxylic acid ethyl ester are obtained in the form of a yellow oil. The 1-[2-(chroman-3-yl)ethyl]-piperidine-3-carboxylic acid ethyl ester hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from acetone/diethyl ether using 0.18 equivalent of water of crystallisation and melts at 140°-143°.

Workup

  1. temperatureafter cooling
  2. concentrationis concentrated by evaporation under a high vacuum
  3. additionWater is added to the oily residue and extraction
  4. extractionThe combined organic phases are extracted with 2N hydrochloric acid
  5. extractionwhile cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane
  6. dry with materialThe combined dichloromethane phases are dried over sodium sulphate
  7. concentrationconcentrated by evaporation in vacuo

Sources & evidence

ORD record
ord-7e833f6e935a483680b658eb09c019fd
Source dataset
uspto-grants-1990_09
Patent number
US04957928

Reaction notes

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