Sodium Chloride → (2S,3R)-2-(Pyridin-3-ylmethyl)quinuclidin-3-amine

HRID 82429Notes

Reaction equation

C1(C)C=CC(C([C@](C(O)=O)(O)[C@](C(C2C=CC(C)=CC=2)=O)(O)C(O)=O)=O)=CC=1.[NH2:29][C@@H:30]1[CH:35]2[CH2:36][CH2:37][N:32]([CH2:33][CH2:34]2)[C@H:31]1[CH2:38][C:39]1[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=1.[Cl-].[Na+].[OH-].[Na+]>>[NH2:29][C@@H:30]1[CH:35]2[CH2:34][CH2:33][N:32]([CH2:37][CH2:36]2)[C@H:31]1[CH2:38][C:39]1[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=1

Participants

Reactant 3

HCID 5234Sodium Chloride

HCID 14798Sodium Hydroxide

HCID 131729022(2S,3R)-3-amino-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octane di-p-toluoyl-D-tartrate salt

Product 1

HCID 25177374(2S,3R)-2-(Pyridin-3-ylmethyl)quinuclidin-3-amineYield 98.1%

Procedure

(2S,3R)-3-Amino-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octane di-p-toluoyl-D-tartrate salt (3.64 kg, 5.96 mol) and 10% aqueous sodium chloride solution (14.4 L, 46.4 mol) were added to a 72 L glass reaction flask equipped with a mechanical stirrer under an inert atmosphere. 5 M Sodium hydroxide (5.09 L) was added to the stirring mixture to adjust the pH of the mixture to pH 14. The mixture was then stirred for a minimum of 10 min. The aqueous solution was extracted with chloroform (4×12.0 L), and the combined organic layers were dried over anhydrous sodium sulfate (1.72 kg). The combined organic layers were filtered, and the filtrate was concentrated to obtain (2S,3R)-3-amino-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octane (1.27 kg) as an oil.

Workup

customequipped with a mechanical stirrer under an inert atmosphere
extractionThe aqueous solution was extracted with chloroform (4×12.0 L)
dry with materialthe combined organic layers were dried over anhydrous sodium sulfate (1.72 kg)
filtrationThe combined organic layers were filtered
concentrationthe filtrate was concentrated

Sources & evidence

ORD record: ord-24893a7d226941b8afa9912b974c8a43
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846715B2

Reaction notes

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