2-Bromo-2',4'-difluoroacetophenone → (R)-1-[2-(2,4-difluoro-phenyl)-2-oxo-ethyl]-3-(2-phenyl-2-phenylamino-acetoxy)-1-azonia-bicyclo[2.2.2]octane bromide

HRID 77033

Reaction equation

HRID 77033 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([O:9][C:10](=[O:25])[C@@H:11]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:2]2.[Br:26][CH2:27][C:28]([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=1[F:37])=[O:29]>C(#N)C>[Br-:26].[F:37][C:31]1[CH:32]=[C:33]([F:36])[CH:34]=[CH:35][C:30]=1[C:28](=[O:29])[CH2:27][N+:1]12[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]1)[C@@H:3]([O:9][C:10](=[O:25])[CH:11]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:2]2

Participants

4

Reactant 2

HCID 27741852-Bromo-2',4'-difluoroacetophenoneHCID 46840261(R)-((R)-quinuclidin-3-yl) 2-phenyl-2-(phenylamino)acetate

Product 1

HCID 46842122(R)-1-[2-(2,4-difluoro-phenyl)-2-oxo-ethyl]-3-(2-phenyl-2-phenylamino-acetoxy)-1-azonia-bicyclo[2.2.2]octane bromideYield 44%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-phenyl-phenylamino-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester (Diastereoisomer 1 of C2) (50 mg, 0.15 mmol) in acetonitrile (1 mL), is added 2-bromo-1-(2,4-difluoro-phenyl)-ethanone (35 mg, 0.15 mmol) and the mixture reacted in a closed vessel under MW irradiation for 1 hour at 100° C. (UPLC-MS monitoring: complete conversion). The solvent is evaporated and the resulting crude is purified by flash chromatography (DCM/MeOH=95/5) to obtain the title compound as a white solid (37.3 mg, 44% yield, bromide salt, single diastereoisomer).

Workup

  1. customthe mixture reacted in a closed vessel under MW irradiation for 1 hour at 100° C. (UPLC-MS monitoring: complete conversion)
  2. customThe solvent is evaporated
  3. customthe resulting crude is purified by flash chromatography (DCM/MeOH=95/5)

Sources & evidence

ORD record
ord-79b62d83923b4c42b9f8a81a4900c86b
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Linked notes

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