Sodium Iodide → 1-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-3-methoxycarbonyl-quinuclidinium hydroxide

HRID 1420645

Reaction equation

HRID 1420645 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]1=2.[CH3:20][O:21][C:22]([CH:24]1[CH:29]2[CH2:30][CH2:31][N:26]([CH2:27][CH2:28]2)[CH2:25]1)=[O:23].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CC(=O)CC.O.C1(C)C=CC=CC=1>[OH-:21].[CH:16]1[C:7]2[CH2:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:5]([CH2:4][CH2:3][CH2:2][N+:26]34[CH2:31][CH2:30][CH:29]([CH2:28][CH2:27]3)[CH:24]([C:22]([O:21][CH3:20])=[O:23])[CH2:25]4)[C:6]=2[CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 2867795-(3-Chloropropyl)-10,11-dihydro-5H-dibenz[b,f]azepineHCID 2736953Methyl quinuclidine-3-carboxylate

Product 1

HCID 229983151-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-3-methoxycarbonyl-quinuclidinium hydroxideYield 108.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6569Methyl Ethyl KetoneSolvent

Procedure

5-(3-Chloropropyl)-10,11-dihydro-5H-dibenzo[b,f]azepine (1.70 g, 6.25 mmol, prepared as described in example 1), and quinuclidine-3-carboxylic acid methyl ester (0.85 g, 5.0 mmol) were dissolved in 2-butanone (25 ml). Dry potassium carbonate (4.15 g, 30 mmol) and sodium iodide (0.75 g, 5 mmol) were added and the stirred mixture was heated at reflux temperature for 5 h. After cooling to room temperature, toluene (25 ml) and water (25 ml) were added. An oily precipitate was formed, which was separated from the solvents by decanting and dissolved in dichloromethane (30 ml). The solution was washed with water (2×30 ml), 1 N hydrochloric acid (2×30 ml), saturated sodium hydrogencarbonate solution (30 ml) and water (30 ml). The organic layer was dried over MgSO4. Evaporation in vacuo afforded 1.15 g 1-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-3-methoxycarbonyl-quinuclidinium hydroxide. The crude product was directly used in the next step without further purification.

Workup

  1. temperaturethe stirred mixture was heated
  2. temperatureat reflux temperature for 5 h
  3. customAn oily precipitate was formed
  4. customwhich was separated from the solvents
  5. customby decanting
  6. dissolutiondissolved in dichloromethane (30 ml)
  7. washThe solution was washed with water (2×30 ml), 1 N hydrochloric acid (2×30 ml), saturated sodium hydrogencarbonate solution (30 ml) and water (30 ml)
  8. dry with materialThe organic layer was dried over MgSO4
  9. customEvaporation in vacuo

Sources & evidence

ORD record
ord-5027d5f38fe74af6bfc6c3c0a688ebd5
Source dataset
uspto-grants-2000_06
Patent number
US06071901

Linked notes

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