2-Chloroacetophenone → (3R)-3-(2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetoxy)-1-(2-oxo-2-phenylethyl)-1-azoniabicyclo[2.2.2]octane chloride

HRID 469471Notes

Reaction equation

HRID 469471 reaction equation
[Cl:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].[S:11]1[CH:15]=[CH:14][C:13]2[CH:16]=[CH:17][CH:18]=[C:19]([CH:20]([NH:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:21]([O:23][C@@H:24]3[CH:29]4[CH2:30][CH2:31][N:26]([CH2:27][CH2:28]4)[CH2:25]3)=[O:22])[C:12]1=2>CCOC(C)=O>[Cl-:1].[S:11]1[CH:15]=[CH:14][C:13]2[CH:16]=[CH:17][CH:18]=[C:19]([CH:20]([NH:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:21]([O:23][C@@H:24]3[CH:29]4[CH2:28][CH2:27][N+:26]([CH2:2][C:3](=[O:4])[C:5]5[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=5)([CH2:31][CH2:30]4)[CH2:25]3)=[O:22])[C:12]1=2

Participants

4

Reactant 2

HCID 107572-ChloroacetophenoneHCID 58557003(R)-quinuclidin-3-yl 2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetate

Product 1

HCID 86660327(3R)-3-(2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetoxy)-1-(2-oxo-2-phenylethyl)-1-azoniabicyclo[2.2.2]octane chlorideYield 21.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2-Chloro-1-phenylethanone (35.4 mg, 0.23 mmol) was added to a solution of (R)-quinuclidin-3-yl 2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetate (C27) (90 mg, 0.23 mmol) in EtOAc (3 ml). The reaction was stirred at room temperature overnight. The solvent was removed under vacuum and the crude was triturated with Et2O. The compound was purified by preparative HPLC (Eluent: CH3CN/H2O) to obtain (3R)-3-(2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetoxy)-1-(2-oxo-2-phenylethyl)-1-azoniabicyclo[2.2.2]octane chloride (26.6 mg, 21.2% yield).

Workup

  1. customThe solvent was removed under vacuum
  2. customthe crude was triturated with Et2O
  3. customThe compound was purified by preparative HPLC (Eluent: CH3CN/H2O)

Sources & evidence

ORD record
ord-68cca16f0d7c42b59403b3fce920524d
Source dataset
uspto-grants-2014_01
Patent number
US08629160B2

Reaction notes

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