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

HRID 1196045Notes

Reaction equation

HRID 1196045 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 esterYield 67%

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 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

Sources & evidence

ORD record
ord-9bd4052b8b48434f97c3aa8ea3673388
Source dataset
uspto-grants-1992_05
Patent number
US05112855

Reaction notes

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