Diisopropylethylamine → 1-(Benzo-1,4-dioxan-2-ylmethyl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester

HRID 1196013

Reaction equation

HRID 1196013 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.Br[CH2:22][CH:23]1[O:28][C:27]2[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=2[O:25][CH2:24]1>CN(C)C=O>[CH3:2][O:3][C:4]([C:6]1[CH2:7][N:8]([CH2:22][CH:23]2[O:28][C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[O:25][CH2:24]2)[CH2:9][CH2:10][CH:11]=1)=[O:5]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 983332-Bromomethyl-1,4-benzodioxaneHCID 15560296Guvacoline Hydrobromide

Product 1

HCID 148384171-(Benzo-1,4-dioxan-2-ylmethyl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl esterYield 74.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

First 11.1 g (50 mmol) of 1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester hydrobromide (guvacoline hydrobromide) and then 22.6 g (175 mmol) of N-ethyl-N,N-diisopropylamine are added to a solution of 11.45 g (50 mmol) of 2-bromomethylbenzo-1,4-dioxan (U.S. Pat. No. 2,366,102) in 100 ml of absolute dimethylformamide. The mixture is stirred for 16 hours at 50° and then concentrated by evaporation under a high vacuum. Water is added to the residue and extraction is carried out with diethyl ether. The organic phases are washed with water and extracted by shaking 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. 10.75 g (74.4%) of 1-(benzo-1,4-dioxan-2-ylmethyl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester are obtained in the form of a yellow oil. The 1-(benzo-1,4-dioxan-2-ylmethyl)-1,2,5,6-tetrahydropyridine- 3-carboxylic acid methyl ester hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from methanol/diethyl ether and decomposes at 215°-217°.

Workup

  1. concentrationconcentrated by evaporation under a high vacuum
  2. additionWater is added to the residue and extraction
  3. washThe organic phases are washed with water
  4. extractionextracted
  5. stirringby shaking with 2N hydrochloric acid
  6. extractionwhile cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane
  7. dry with materialThe combined dichloromethane phases are dried over sodium sulphate
  8. concentrationconcentrated by evaporation in vacuo

Sources & evidence

ORD record
ord-84e6bacaebb74337bc6ef20752fd9726
Source dataset
uspto-grants-1992_05
Patent number
US05112855

Linked notes

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