Phenacyl bromide → (3R)-3-(2-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)acetoxy)-1-(2-oxo-2-phenylethyl)-1-azoniabicyclo[2.2.2]octane bromide

HRID 1619529Notes

Reaction equation

HRID 1619529 reaction equation
[Br:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].[C:11]([O:15][C:16]([NH:18][CH:19]([C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)[C:20]([O:22][C@@H:23]1[CH:28]2[CH2:29][CH2:30][N:25]([CH2:26][CH2:27]2)[CH2:24]1)=[O:21])=[O:17])([CH3:14])([CH3:13])[CH3:12]>CCOC(C)=O>[Br-:1].[C:11]([O:15][C:16]([NH:18][CH:19]([C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)[C:20]([O:22][C@@H:23]1[CH:28]2[CH2:27][CH2:26][N+:25]([CH2:2][C:3](=[O:4])[C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)([CH2:30][CH2:29]2)[CH2:24]1)=[O:21])=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

4

Reactant 2

HCID 6259Phenacyl bromide3×HCID 67607091HCID 67607091, compound

Product 1

HCID 86665838(3R)-3-(2-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)acetoxy)-1-(2-oxo-2-phenylethyl)-1-azoniabicyclo[2.2.2]octane bromideYield 42.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2-Bromo-1-phenylethanone (55.4 mg, 0.28 mmol) was added to a solution of (R)-quinuclidin-3-yl 2-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)acetate (C47) (100 mg, 0.25 mmol) in EtOAc (3 ml). The reaction was stirred at RT for 36 hours, and then a second portion of 2-bromo-1-phenylethanone (50.4 mg, 0.25 mmol) was added, and the reaction was stirred at RT for additional 48 hours. The organic phase was washed with aq. Na2CO3, dried over Na2SO4 and evaporated. The crude was dissolved in acetonitrile (3 ml), and 2-bromo-1-phenylethanone (60.0 mg, 0.30 mmol) was added. The reaction was heated under microwave irradiation at 100° C. for 45 minutes. The solvent was evaporated and the crude was purified by flash chromatography (DCM/MeOH=95/5 to 9/1) to obtain (3R)-3-(2-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)acetoxy)-1-(2-oxo-2-phenylethyl)-1-azoniabicyclo[2.2.2]octane bromide (62.5 mg; 42% yield).

Workup

  1. stirringthe reaction was stirred at RT for additional 48 hours
  2. washThe organic phase was washed with aq. Na2CO3
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. dissolutionThe crude was dissolved in acetonitrile (3 ml)
  6. temperatureThe reaction was heated under microwave irradiation at 100° C. for 45 minutes
  7. customThe solvent was evaporated
  8. customthe crude was purified by flash chromatography (DCM/MeOH=95/5 to 9/1)

Sources & evidence

ORD record
ord-5f13bec1cb574863af09edd93fd20d8b
Source dataset
uspto-grants-2014_07
Patent number
US08772314B2

Reaction notes

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