Diisopropylethylamine → 1-[2-(Chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester

HRID 1196017Notes

Reaction equation

HRID 1196017 reaction equation
Cl.[CH2:2]([O:4][C:5]([C:7]1[CH2:8][NH:9][CH2:10][CH2:11][CH:12]=1)=[O:6])[CH3:3].C(N(C(C)C)C(C)C)C.C1(C)C=CC(S(O[CH2:32][CH2:33][CH:34]2[CH2:43][C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[O:36][CH2:35]2)(=O)=O)=CC=1>CN(C)C=O>[CH2:2]([O:4][C:5]([C:7]1[CH2:8][N:9]([CH2:32][CH2:33][CH:34]2[CH2:43][C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[O:36][CH2:35]2)[CH2:10][CH2:11][CH:12]=1)=[O:6])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 205700Ethyl 1,2,5,6-tetrahydropyridine-3-carboxylate hydrochlorideHCID 148384153-[2-(p-Toluenesulphonyloxy)ethyl]chroman

Product 1

HCID 148384331-[2-(Chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl esterYield 52.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

First 2.1 g (11 mmol) of 1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester hydrochloride and then 4.53 g (35 mmol) of N-ethyl-N,N-diisopropylamine are added to a solution of 3.32 g (10 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. 1.65 g (52.3%) of 1-[2-(chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester are obtained in the form of a yellow oil. The 1-[2-(chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from acetone/diethyl ether and melts at 177°-178°.

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-9519091f1d634594a9e5dd80784fddc7
Source dataset
uspto-grants-1992_05
Patent number
US05112855

Reaction notes

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