Sodium Iodide → (R)-1-[3-(tert-Butoxycarbonyl-methyl-amino)-propyl]-3-(2-hydroxy-2,2-diphenyl-acetoxy)-1-azonia-bicyclo[2.2.2]octane chloride

HRID 1920562Notes

Reaction equation

HRID 1920562 reaction equation
[C:1]([O:5][C:6](=[O:13])[N:7]([CH2:9][CH2:10][CH2:11][Cl:12])[CH3:8])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[N:23]12[CH2:30][CH2:29][CH:26]([CH2:27][CH2:28]1)[C@@H:25]([O:31][C:32](=[O:47])[C:33]([OH:46])([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:24]2.C([O-])([O-])=O.[K+].[K+].[I-].[Na+]>CN(C=O)C>[Cl-:12].[C:1]([O:5][C:6]([N:7]([CH3:8])[CH2:9][CH2:10][CH2:11][N+:23]12[CH2:28][CH2:27][CH:26]([CH2:29][CH2:30]1)[C@@H:25]([O:31][C:32](=[O:47])[C:33]([OH:46])([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH2:24]2)=[O:13])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium Carbonate2×HCID 81531DiisopropylethylamineHCID 688566Quinuclidinyl benzilate, (-)-HCID 14194551tert-Butyl (3-chloropropyl)methylcarbamate

Product 1

HCID 67496766(R)-1-[3-(tert-Butoxycarbonyl-methyl-amino)-propyl]-3-(2-hydroxy-2,2-diphenyl-acetoxy)-1-azonia-bicyclo[2.2.2]octane chloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

(3-Chloro-propyl)-methyl-carbamic acid tert-butyl ester (2.00 g 9.629 mmol) is solubilised in DMF (20 ml) and polystyrene bound DIPEA added, and after a few minutes removed. This solution is then added to a mixture of hydroxy-diphenyl-acetic acid (R)-(1-aza-bicyclo [2.2.2]oct-3-yl) ester (2.1634 g 6.419 mmol) and 200 mg of K2CO3, followed by the addition of sodium iodide (10 mg) and heating at 60° C. for 2 days. 2.5 g Merrifield resin and 100 mg K2CO3 is then added to the mixture and heating resumed at 40° C. for 12 hours. The resin is then removed, and the mixture purified by gradient C18 column chromatography to give the title product.

Workup

  1. additionadded
  2. customafter a few minutes removed
  3. temperatureheating
  4. customThe resin is then removed
  5. customthe mixture purified by gradient C18 column chromatography

Sources & evidence

ORD record
ord-0c52665c7f1d4d52ad184cca89a53550
Source dataset
uspto-grants-2012_05
Patent number
US08168654B2

Reaction notes

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