Water → N-(1-Azabicyclo[2.2.2]oct-3-yl)-2,4-dimethoxybenzamide hydrochloride

HRID 3761

Reaction equation

HRID 3761 reaction equation
Cl.Cl.[NH2:3][CH:4]1[CH:9]2[CH2:10][CH2:11][N:6]([CH2:7][CH2:8]2)[CH2:5]1.[CH3:12][O:13][C:14]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:15]=1[C:16]([Cl:18])=[O:17].C(=O)([O-])[O-].[Na+].[Na+].O>C(Cl)(Cl)Cl>[ClH:18].[N:6]12[CH2:11][CH2:10][CH:9]([CH2:8][CH2:7]1)[CH:4]([NH:3][C:16](=[O:17])[C:15]1[CH:19]=[CH:20][C:21]([O:23][CH3:24])=[CH:22][C:14]=1[O:13][CH3:12])[CH2:5]2

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 197853Quinuclidine, 3-amino-, dihydrochlorideHCID 27347192,4-Dimethoxybenzoyl chloride

Product 1

HCID 13272330N-(1-Azabicyclo[2.2.2]oct-3-yl)-2,4-dimethoxybenzamide hydrochlorideYield 23.7%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of 3-aminoquinuclidine dihydrochloride, 6.95 g, (0.349), 2,4-dimethoxybenzoyl chloride, 700 g, (0.0349 mole), anhydrous sodium carbonate, 36.99 g, (0.349 mole), 175 ml water, and 175 ml chloroform was stirred rapidly to achieve good mixing of the 2 layers for 20 hrs. The chloroform layer was then separated, washed with water, dried over anhydrous magnesium sulfate, and concentrated to an impure oil. The oil was triturated twice with 20 ml portions of petroleum ether to remove some impurities. The oil was then dissolved in diethyl ether and filtered to remove a small amount of insoluble material. The filtrate was treated with ethereal hydrogen chloride and the resulting salt collected to yield 2.70 g (23.7% yield) white solid. The salt was recrystallized from ethanol-isopropyl ether. Further recrystallization from methanol-ethyl ether yielded a white solid, m.p. 211°-212° C. The NMR analysis was satisfactory.

Workup

  1. additionto achieve good mixing of the 2 layers for 20 hrs
  2. customThe chloroform layer was then separated
  3. washwashed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated to an impure oil
  6. customThe oil was triturated twice with 20 ml portions of petroleum ether
  7. customto remove some impurities
  8. dissolutionThe oil was then dissolved in diethyl ether
  9. filtrationfiltered
  10. customto remove a small amount of insoluble material
  11. additionThe filtrate was treated with ethereal hydrogen chloride
  12. customthe resulting salt collected

Sources & evidence

ORD record
ord-217b10af343044bfa5761f4da10eaeb8
Source dataset
uspto-grants-1988_02
Patent number
US04722834

Linked notes

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