4-(Chloromethyl)-2-phenyl-1,3-oxazole → (3R)-3-(2-phenyl-2-(piperidin-1-yl)acetoxy)-1-((2-phenyloxazol-4-yl)methyl)-1-azoniabicyclo[2.2.2]octane chloride

HRID 404622

Reaction equation

HRID 404622 reaction equation
[C:1]1([CH:7]([N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:8]([O:10][C@@H:11]2[CH:16]3[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]3)[CH2:12]2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:25][CH2:26][C:27]1[N:28]=[C:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:30][CH:31]=1>CCOC(C)=O.C(#N)C>[Cl-:25].[C:1]1([CH:7]([N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:8]([O:10][C@@H:11]2[CH:16]3[CH2:17][CH2:18][N+:13]([CH2:26][C:27]4[N:28]=[C:29]([C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=5)[O:30][CH:31]=4)([CH2:14][CH2:15]3)[CH2:12]2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 35511964-(Chloromethyl)-2-phenyl-1,3-oxazoleHCID 71603247(R)-quinuclidin-3-yl 2-phenyl-2-(piperidin-1-yl)acetate

Product 1

HCID 86688883(3R)-3-(2-phenyl-2-(piperidin-1-yl)acetoxy)-1-((2-phenyloxazol-4-yl)methyl)-1-azoniabicyclo[2.2.2]octane chlorideYield 35.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-quinuclidin-3-yl 2-phenyl-2-(piperidin-1-yl)acetate (100 mg, 0.30 mmol) in EtOAc (2 ml) and acetonitrile (1 ml), was added 4-(chloromethyl)-2-phenyloxazole (70.7 mg, 0.36 mmol). The reaction was stirred at room temperature for 30 hours and then the solvents were evaporated. Purification by flash chromatography (DCM/MeOH=9/1) followed by trituration with Et2O afforded (3R)-3-(2-phenyl-2-(piperidin-1-yl)acetoxy)-1-((2-phenyloxazol-4-yl)methyl)-1-azoniabicyclo[2.2.2]octane chloride (55 mg, 34.6% yield) as an off-white solid.

Workup

  1. customthe solvents were evaporated
  2. customPurification by flash chromatography (DCM/MeOH=9/1)

Sources & evidence

ORD record
ord-df65fa96c2e449f494d5b424559754fc
Source dataset
uspto-grants-2014_06
Patent number
US08748613B2

Linked notes

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