2-(Chloroacetyl)thiophene → (R)-3-[2-(4-methyl-benzylamino)-2-phenyl-acetoxy]-1-(2-oxo-2-thiophen-2-yl-ethyl)-1-azonia-bicyclo[2.2.2]octane formate formate

HRID 77043Notes

Reaction equation

HRID 77043 reaction equation
[CH3:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][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])=[CH:4][CH:3]=1.Cl[CH2:29][C:30]([C:32]1[S:33][CH:34]=[CH:35][CH:36]=1)=[O:31]>C(OCC)(=O)C>[CH:9]([O-:11])=[O:10].[CH:9]([O-:11])=[O:10].[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][CH:8]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:9]([O:11][C@@H:12]2[CH:17]3[CH2:16][CH2:15][N+:14]([CH2:29][C:30](=[O:31])[C:32]4[S:33][CH:34]=[CH:35][CH:36]=4)([CH2:19][CH2:18]3)[CH2:13]2)=[O:10])=[CH:26][CH:27]=1.[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][CH:8]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:9]([O:11][C@@H:12]2[CH:17]3[CH2:16][CH2:15][N+:14]([CH2:29][C:30]([C:32]4[S:33][CH:34]=[CH:35][CH:36]=4)=[O:31])([CH2:19][CH2:18]3)[CH2:13]2)=[O:10])=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 27579252-(Chloroacetyl)thiopheneHCID 59401115(R)-Quinuclidin-3-yl 2-(4-methylbenzylamino)-2-phenylacetate

Product 1

HCID 86643230(R)-3-[2-(4-methyl-benzylamino)-2-phenyl-acetoxy]-1-(2-oxo-2-thiophen-2-yl-ethyl)-1-azonia-bicyclo[2.2.2]octane formate formateYield 78.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(R)-Quinuclidin-3-yl 2-(4-methylbenzylamino)-2-phenylacetate (C77) (73 mg, 0.20 mmol) is dissolved in ethyl acetate (2.00 mL) and 2-chloro-1-(thiophen-2-yl)ethanone (35.4 mg, 0.22 mmol) is added. The colorless solution is stirred at RT overnight. Solvent is evaporated and the residue is first purified by flash chromatography (DCM/MeOH=9/1 to 85/15) and then by preparative LC/MS. Organic solvent is evaporated and then the aqueous solution is freeze-dried overnight to afford the title compound as a pale yellow oil (42 mg, 36% yield, formate formate anion, mixture of diastereoisomers).

Workup

  1. customSolvent is evaporated
  2. customthe residue is first purified by flash chromatography (DCM/MeOH=9/1 to 85/15)
  3. customOrganic solvent is evaporated
  4. customthe aqueous solution is freeze-dried overnight

Sources & evidence

ORD record
ord-30c89b118ea64801a4714a22fdf520fe
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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