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

HRID 1032426Notes

Reaction equation

HRID 1032426 reaction equation
Br.[CH3:2][O:3][C:4]([C:6]1[CH2:7][NH:8][CH2:9][CH2:10][CH:11]=1)=[O:5].C(N(C(C)C)C(C)C)C.[CH3:21][C:22]1([CH3:45])[CH:31]([CH2:32][CH2:33]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[O:23]1>CN(C)C=O>[CH3:2][O:3][C:4]([C:6]1[CH2:7][N:8]([CH2:33][CH2:32][CH:31]2[CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[O:23][C:22]2([CH3:21])[CH3:45])[CH2:9][CH2:10][CH:11]=1)=[O:5]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 15560296Guvacoline HydrobromideHCID 540378412,2-Dimethyl-3-[2-(4-toluenesulfonyloxy)ethyl]-chroman

Product 1

HCID 539181401-[2-(2,2-Dimethylchroman-3-yl)-ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

First 5.55 g (25 mmol) of 1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester hydrobromide (guvacoline hydrobromide) and then 11.31 g (87.5 mmol) of N-ethyl-N,N-diisopropyl-amine are added to a solution of 9 g (25 mmol) of 2,2-dimethyl-3-[2-(4-toluenesulfonyloxy)ethyl]-chroman in 100 ml of N,N-dimethylformamide. The solution is stirred for 15 hours at 60° and then concentrated by evaporation under a high vacuum. Water is added to the residue and extraction is carried out with diethyl ether. The combined organic phases are washed with water and extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline with sodium hydroxide solution (30%) while cooling and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulfate and concentrated by evaporation in vacuo, yielding 5.52 g (67% of the theoretical yield) of 1-[2-(2,2-dimethylchroman-3-yl)-ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester in the form of a light-yellow oil. 1-[2-(2,2-dimethylchroman-3-yl)-ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester hydrochloride, prepared therefrom with hydrochloric acid in diethyl ether, crystallises from methanol/diethyl ether and melts at 196°-197°.

Workup

  1. concentrationconcentrated by evaporation under a high vacuum
  2. additionWater is added to the residue and extraction
  3. washThe combined organic phases are washed with water
  4. extractionextracted with 2N hydrochloric acid
  5. temperaturewhile cooling
  6. extractionextracted with dichloromethane
  7. dry with materialThe combined dichloromethane phases are dried over sodium sulfate
  8. concentrationconcentrated by evaporation in vacuo
  9. customyielding 5.52 g (67% of the

Sources & evidence

ORD record
ord-7c5ea9397eb54d54b3d547450a666c77
Source dataset
uspto-grants-1990_09
Patent number
US04957928

Reaction notes

Loading…