Diethyl Ether → (R)-3-[2-(4-fluoro-benzylamino)-2-phenyl-acetoxy]-1-(2-oxo-2-thiophen-2-yl-ethyl)-1-azonia-bicyclo[2.2.2]octane chloride

HRID 77045Notes

Reaction equation

HRID 77045 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:9]([O:11][C@@H:12]2[CH:17]3[CH2:18][CH2:19][N:14]([CH2:15][CH2:16]3)[CH2:13]2)=[O:10])=[CH:4][CH:3]=1.[Cl:28][CH2:29][C:30]([C:32]1[S:33][CH:34]=[CH:35][CH:36]=1)=[O:31].CCOCC>C(OCC)(=O)C>[Cl-:28].[F:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][CH:8]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:9]([O:11][C@@H:12]2[CH:17]3[CH2:16][CH2:15][N+:14]([CH2:29][C:30](=[O:31])[C:32]4[S:33][CH:34]=[CH:35][CH:36]=4)([CH2:19][CH2:18]3)[CH2:13]2)=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 27579252-(Chloroacetyl)thiopheneHCID 59401102(R)-Quinuclidin-3-yl 2-(4-fluorobenzylamino)-2-phenylacetate

Product 1

HCID 86643233(R)-3-[2-(4-fluoro-benzylamino)-2-phenyl-acetoxy]-1-(2-oxo-2-thiophen-2-yl-ethyl)-1-azonia-bicyclo[2.2.2]octane chlorideYield 68.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(R)-Quinuclidin-3-yl 2-(4-fluorobenzylamino)-2-phenylacetate (C78) (85 mg, 0.23 mmol) is dissolved in ethyl acetate (2.31 mL) and 2-chloro-1-(thiophen-2-yl)ethanone (40.8 mg, 0.25 mmol) is added. The solution is stirred at RT overnight. The suspension is evaporated and the white residue is first purified by flash chromatography (DCM/MeOH=9/1 to 8/2) and then by trituration with Et2O to afford the title compound as an off-white powder (83 mg, 68% yield, chloride salt, mixture of diastereoisomers).

Workup

  1. customThe suspension is evaporated
  2. customthe white residue is first purified by flash chromatography (DCM/MeOH=9/1 to 8/2)

Sources & evidence

ORD record
ord-4ad19121a6ce4ccf88a864aaf064938e
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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