2-(Chloroacetyl)thiophene → (R)-3-[(R)-2-(4-fluoro-phenylamino)-2-phenyl-acetoxy]-1-(2-oxo-2-thiophen-2-yl-ethyl)-1-azonia-bicyclo[2.2.2]octane chloride

Participants

Role	Name	HCID	Charge
Reactant	2-(Chloroacetyl)thiophene	HCID 2757925	—
Reactant	(R)-((R)-quinuclidin-3-yl) 2-(4-fluorophenylamino)-2-phenylacetate	HCID 59401133	—
Solvent	Acetonitrile	HCID 6342	—
Product	(R)-3-[(R)-2-(4-fluoro-phenylamino)-2-phenyl-acetoxy]-1-(2-oxo-2-thiophen-2-yl-ethyl)-1-azonia-bicyclo[2.2.2]octane chloride	HCID 86691137	36.1%

Reaction Conditions

Temperature	100 °C

Reaction Steps

To a solution of (R)-(4-fluoro-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester (C254) (200 mg, 0.56 mmol) in CH3CN (2 mL), is added 2-chloro-1-(thiophen-2-yl)ethanone (100 mg, 0.62 mmol). The reaction is heated at 100° C. for 1 hour under MW irradiation. The solvent is evaporated and the crude is purified by flash chromatography (DCM/MeOH=9/1) recovering the title compound as a white solid (104 mg, 36% yield, chloride salt, single diastereoisomer).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08835682B2
Source dataset	uspto-grants-2014_09
ORD ID	ord-f53907ddbd6c456284b8004ed12b20e8
Source note	uspto-grants-2014_09