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

HRID 77044Notes

Reaction equation

HRID 77044 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][NH:8][CH:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]([O:12][C@@H:13]2[CH:18]3[CH2:19][CH2:20][N:15]([CH2:16][CH2:17]3)[CH2:14]2)=[O:11])=[CH:5][CH:4]=1.Cl[CH2:30][C:31]([C:33]1[S:34][CH:35]=[CH:36][CH:37]=1)=[O:32]>C(OCC)(=O)C>[CH:10]([O-:12])=[O:11].[CH:10]([O-:12])=[O:11].[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][CH:9]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:10]([O:12][C@@H:13]2[CH:18]3[CH2:17][CH2:16][N+:15]([CH2:30][C:31](=[O:32])[C:33]4[S:34][CH:35]=[CH:36][CH:37]=4)([CH2:20][CH2:19]3)[CH2:14]2)=[O:11])=[CH:27][CH:28]=1.[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][CH:9]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:10]([O:12][C@@H:13]2[CH:18]3[CH2:17][CH2:16][N+:15]([CH2:30][C:31]([C:33]4[S:34][CH:35]=[CH:36][CH:37]=4)=[O:32])([CH2:20][CH2:19]3)[CH2:14]2)=[O:11])=[CH:27][CH:28]=1

Participants

4

Reactant 2

HCID 27579252-(Chloroacetyl)thiopheneHCID 59401167(R)-quinuclidin-3-yl 2-(4-methoxybenzylamino)-2-phenylacetate

Product 1

HCID 86643232(R)-3-[2-(4-methoxy-benzylamino)-2-phenyl-acetoxy]-1-(2-oxo-2-thiophen-2-yl-ethyl)-1-azonia-bicyclo[2.2.2]octane formate formateYield 76.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-quinuclidin-3-yl 2-(4-methoxybenzylamino)-2-phenylacetate (C79) (78 mg, 0.21 mmol) in ethyl acetate (2.05 mL), is added 2-chloro-1-(thiophen-2-yl)ethanone (36.2 mg, 0.23 mmol). The colorless solution is stirred at RT overnight. The residue is first purified by flash chromatography (DCM/MeOH=90/10 to 85/15) and then by preparative LC/MS. MeOH is evaporated from the fractions collected and then the aqueous solution is freeze-dried overnight to obtain the title compound as a pale pink oil (44 mg, 36% yield, formate formate anion, mixture of diastereoisomers).

Workup

  1. customThe residue is first purified by flash chromatography (DCM/MeOH=90/10 to 85/15)
  2. customMeOH is evaporated from the fractions
  3. customcollected
  4. customthe aqueous solution is freeze-dried overnight

Sources & evidence

ORD record
ord-9ed4cbb6bc4d46c4a8b1e4f887245fe3
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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