2-Chloroacetophenone → (3R)-3-(2-(4-methyl-3-oxopiperazin-1-yl)-2-phenylacetoxy)-1-(2-oxo-2-phenylethyl)-1-azoniabicyclo[2.2.2]octane chloride

HRID 404644Notes

Reaction equation

HRID 404644 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([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])[CH2:4][C:3]1=[O:26].[Cl:27][CH2:28][C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:30]>C(OCC)(=O)C.C(#N)C>[Cl-:27].[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([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[CH2:16][CH2:15][N+:14]([CH2:28][C:29](=[O:30])[C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)([CH2:19][CH2:18]3)[CH2:13]2)=[O:10])[CH2:4][C:3]1=[O:26]

Participants

5

Reactant 2

HCID 107572-ChloroacetophenoneHCID 86688902(R)-quinuclidin-3-yl 2-(4-methyl-3-oxopiperazin-1-yl)-2-phenylacetate

Product 1

HCID 86688903(3R)-3-(2-(4-methyl-3-oxopiperazin-1-yl)-2-phenylacetoxy)-1-(2-oxo-2-phenylethyl)-1-azoniabicyclo[2.2.2]octane chlorideYield 41.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

(R)-Quinuclidin-3-yl 2-(4-methyl-3-oxopiperazin-1-yl)-2-phenylacetate (169 mg, 0.47 mmol) was dissolved in a mixture of ethyl acetate (3 ml) and acetonitrile (1.5 ml). 2-Chloro-1-phenylethanone (80 mg, 0.52 mmol) was added and the reaction was stirred at room temperature for 5 hours. The solvent was evaporated and the residue was triturated with EtOAc (10 ml). The product was purified by flash chromatography (DCM/MeOH=9/1 to 85/15) to obtain (3R)-3-(2-(4-methyl-3-oxopiperazin-1-yl)-2-phenylacetoxy)-1-(2-oxo-2-phenylethyl)-1-azoniabicyclo[2.2.2]octane chloride (99 mg, 0.193 mmol, 40.9% yield) as a pale yellow spongy solid.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was triturated with EtOAc (10 ml)
  3. customThe product was purified by flash chromatography (DCM/MeOH=9/1 to 85/15)

Sources & evidence

ORD record
ord-21bb249a5865426291ba5d7d1d79b1c4
Source dataset
uspto-grants-2014_06
Patent number
US08748613B2

Reaction notes

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