2-(Chloroacetyl)thiophene → (3R)-3-(2-(3-(ethoxycarbonyl)phenylamino)-2-(6-methoxypyridin-3-yl)acetoxy)-1-(2-oxo-2-(thiophen-2-yl)ethyl)-1-azoniabicyclo[2.2.2]octane chloride

HRID 469499Notes

Reaction equation

HRID 469499 reaction equation
[Cl:1][CH2:2][C:3]([C:5]1[S:6][CH:7]=[CH:8][CH:9]=1)=[O:4].[CH3:10][O:11][C:12]1[N:17]=[CH:16][C:15]([CH:18]([NH:30][C:31]2[CH:32]=[C:33]([CH:39]=[CH:40][CH:41]=2)[C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:19](=[O:29])[O:20][C@@H:21]2[CH:26]3[CH2:27][CH2:28][N:23]([CH2:24][CH2:25]3)[CH2:22]2)=[CH:14][CH:13]=1>CCOC(C)=O>[Cl-:1].[CH2:37]([O:36][C:34]([C:33]1[CH:32]=[C:31]([NH:30][CH:18]([C:15]2[CH:16]=[N:17][C:12]([O:11][CH3:10])=[CH:13][CH:14]=2)[C:19]([O:20][C@@H:21]2[CH:26]3[CH2:27][CH2:28][N+:23]([CH2:2][C:3](=[O:4])[C:5]4[S:6][CH:7]=[CH:8][CH:9]=4)([CH2:24][CH2:25]3)[CH2:22]2)=[O:29])[CH:41]=[CH:40][CH:39]=1)=[O:35])[CH3:38]

Participants

4

Reactant 2

HCID 27579252-(Chloroacetyl)thiopheneHCID 58556990ethyl 3-(1-(6-methoxypyridin-3-yl)-2-oxo-2-((R)-quinuclidin-3-yloxy)ethylamino)benzoate

Product 1

HCID 86660334(3R)-3-(2-(3-(ethoxycarbonyl)phenylamino)-2-(6-methoxypyridin-3-yl)acetoxy)-1-(2-oxo-2-(thiophen-2-yl)ethyl)-1-azoniabicyclo[2.2.2]octane chlorideYield 63%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2-Chloro-1-(thiophen-2-yl)ethanone (18.3 mg, 0.11 mmol) was added to a solution of ethyl 3-(1-(6-methoxypyridin-3-yl)-2-oxo-2-((R)-quinuclidin-3-yloxy)ethylamino)benzoate (C65) (50 mg, 0.11 mmol) in EtOAc (2 ml). The reaction was stirred at room temperature overnight. The solvent was evaporated, and the residue was triturated with Et2O, filtered and dried. The product was purified by flash-chromatography (DCM/MeOH=97/3 to 9/1) to obtain (3R)-3-(2-(3-(ethoxycarbonyl)phenylamino)-2-(6-methoxypyridin-3-yl)acetoxy)-1-(2-oxo-2-(thiophen-2-yl)ethyl)-1-azoniabicyclo[2.2.2]octane chloride (41.6 mg, 60.9% yield).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was triturated with Et2O
  3. filtrationfiltered
  4. customdried
  5. customThe product was purified by flash-chromatography (DCM/MeOH=97/3 to 9/1)

Sources & evidence

ORD record
ord-5960b4188c144f07b9b23b42d9adb92f
Source dataset
uspto-grants-2014_01
Patent number
US08629160B2

Reaction notes

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