4-Fluorophenethyl bromide → (R)-3-((bis(3-fluorophenyl)-methoxy)carbonylamino)-1-(4-fluorophenethyl)-1-azoniabicyclo[2.2.2]octane bromide

HRID 1910490Notes

Reaction equation

HRID 1910490 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10](=[O:27])[O:11][CH:12]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1)[CH2:2]2.[Br:28][CH2:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1>C(OCC)(=O)C>[Br-:28].[F:26][C:22]1[CH:21]=[C:20]([CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=2)[O:11][C:10]([NH:9][C@@H:3]2[CH:4]3[CH2:7][CH2:8][N+:1]([CH2:29][CH2:30][C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)([CH2:6][CH2:5]3)[CH2:2]2)=[O:27])[CH:25]=[CH:24][CH:23]=1

Participants

4

Reactant 2

HCID 5731534-Fluorophenethyl bromide2×HCID 66575633(R)-bis(3-fluorophenyl)methyl quinuclidin-3-ylcarbamate

Product 1

HCID 70673622(R)-3-((bis(3-fluorophenyl)-methoxy)carbonylamino)-1-(4-fluorophenethyl)-1-azoniabicyclo[2.2.2]octane bromideYield 55.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(R)-bis(3-Fluorophenyl)methyl quinuclidin-3-ylcarbamate (55 mg, 0.14 mmol, prepared as in example 1) was dissolved in ethyl acetate (2 ml), and 1-(2-bromoethyl)-4-fluorobenzene (21 μl, 0.15 mmol) was added. The reaction was stirred at room temperature for 24 hours, then 1-(2-bromoethyl)-4-fluorobenzene (6.21 μl, 0.04 mmol) was added again. After being stirred at room temperature for 2 days, the reaction was concentrated under vacuum, and the crude was first purified by flash chromatography (DCM/MeOH=9/1) and then triturated with DCM/Et2O (1/1) to obtain (R)-3-((bis(3-fluorophenyl)-methoxy)carbonylamino)-1-(4-fluorophenethyl)-1-azoniabicyclo[2.2.2]octane bromide (45 mg).

Workup

  1. stirringAfter being stirred at room temperature for 2 days
  2. concentrationthe reaction was concentrated under vacuum
  3. customthe crude was first purified by flash chromatography (DCM/MeOH=9/1)
  4. customtriturated with DCM/Et2O (1/1)

Sources & evidence

ORD record
ord-5317e96d29064362b6671626b27e8df0
Source dataset
uspto-grants-2013_12
Patent number
US08604015B2

Reaction notes

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