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

HRID 77054Notes

Reaction equation

HRID 77054 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([O:9][C:10](=[O:26])[C@H:11]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:2]2.[Cl:27][CH2:28][C:29]([C:31]1[S:32][CH:33]=[CH:34][CH:35]=1)=[O:30]>CC#N>[Cl-:27].[F:25][C:22]1[CH:21]=[CH:20][C:19]([NH:18][C@H:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:10]([O:9][C@@H:3]2[CH:4]3[CH2:7][CH2:8][N+:1]([CH2:28][C:29](=[O:30])[C:31]4[S:32][CH:33]=[CH:34][CH:35]=4)([CH2:6][CH2:5]3)[CH2:2]2)=[O:26])=[CH:24][CH:23]=1

Participants

4

Reactant 2

HCID 27579252-(Chloroacetyl)thiopheneHCID 59401133(R)-((R)-quinuclidin-3-yl) 2-(4-fluorophenylamino)-2-phenylacetate

Product 1

HCID 86691137(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 chlorideYield 36.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

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).

Workup

  1. customThe solvent is evaporated
  2. customthe crude is purified by flash chromatography (DCM/MeOH=9/1)

Sources & evidence

ORD record
ord-f53907ddbd6c456284b8004ed12b20e8
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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