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

HRID 469472Notes

Reaction equation

HRID 469472 reaction equation
[Cl:1][CH2:2][C:3]([C:5]1[S:6][CH:7]=[CH:8][CH:9]=1)=[O:4].[S:10]1[CH:14]=[CH:13][C:12]2[CH:15]=[CH:16][CH:17]=[C:18]([CH:19]([NH:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:20]([O:22][C@@H:23]3[CH:28]4[CH2:29][CH2:30][N:25]([CH2:26][CH2:27]4)[CH2:24]3)=[O:21])[C:11]1=2.C(Cl)Cl.CO>C(#N)C>[Cl-:1].[S:10]1[CH:14]=[CH:13][C:12]2[CH:15]=[CH:16][CH:17]=[C:18]([CH:19]([NH:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:20]([O:22][C@@H:23]3[CH:28]4[CH2:27][CH2:26][N+:25]([CH2:2][C:3](=[O:4])[C:5]5[S:6][CH:7]=[CH:8][CH:9]=5)([CH2:30][CH2:29]4)[CH2:24]3)=[O:21])[C:11]1=2

Participants

5

Reactant 3

HCID 27579252-(Chloroacetyl)thiopheneHCID 21226129Dichloromethane methanolHCID 58557003(R)-quinuclidin-3-yl 2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetate

Product 1

HCID 86660328(3R)-3-(2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetoxy)-1-(2-oxo-2-(thiophen-2-yl)ethyl)-1-azoniabicyclo[2.2.2]octane chlorideYield 16%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-Chloro-1-(thiophen-2-yl)ethanone (36.8 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 acetonitrile (3 ml). The reaction was stirred at r.t. overnight. The solvent was removed under vacuum, and the crude product was triturated with Et2O. The compound was first purified by preparative HPLC (Eluent: CH3CN/H2O) and then by flash chromatography (DCM/MeOH=95/5) to obtain (3R)-3-(2-(benzo[b]thiophen-7-yl)-2-(phenylamino)acetoxy)-1-(2-oxo-2-(thiophen-2-yl)ethyl)-1-azoniabicyclo[2.2.2]octane chloride (20 mg, 16% yield).

Workup

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

Sources & evidence

ORD record
ord-a41e8da4dc46469092f98f14554f707a
Source dataset
uspto-grants-2014_01
Patent number
US08629160B2

Reaction notes

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