Cesium carbonate → 5-[2-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]ethyl]-5,7-dihydro-6H-pyrido[3,2-a][3]benzazepin-6-one

HRID 1045794Notes

Reaction equation

HRID 1045794 reaction equation
[CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][C:7](=[O:16])[NH:6][C:5]=2[N:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:24][CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]>C(#N)C>[Si:27]([O:26][CH2:25][CH2:24][N:6]1[C:5]2[N:4]=[CH:3][CH:2]=[CH:1][C:11]=2[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[CH2:8][C:7]1=[O:16])([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 712370155,7-Dihydropyrido[2,3-d][3]benzazepin-6-one

Product 1

HCID 712371035-[2-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]ethyl]-5,7-dihydro-6H-pyrido[3,2-a][3]benzazepin-6-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

Add 5,7-dihydropyrido[2,3-d][3]benzazepin-6-one (33.8 g, 0.16 mol) in acetonitrile (340.0 mL) and stir at 20-30° C. for 0.5-1 hour. Add cesium carbonate (104.6 g, 0.32 mol) and (2-bromoethoxy)-tert-butyldimethylsilane (42.2 g, 0.18 mol) and heat the reaction mixture to 70-80° C. for 18-20 hours. Cool the reaction mixture to 20-25° C. and filter through diatomaceous earth (50.6 g). Wash the filter cake with acetonitrile (2×50.6 mL) and concentrate the filtrate under reduced pressure to arrive at a total volume of approximately 67.5 mL. Add toluene (152 mL), active carbon (2.53 g) and heat the mixture to 60-70° C. for 1-2 hours. Cool the mixture to 25-35° C. and filter the reaction mixture over diatomaceous earth (50.6 g). Rinse the filter cake with toluene (17.0 mL) and concentrate under reduced pressure to obtain the title compound as a light brown oil that crystallizes on standing (56.8 g, 92.2%).

Workup

  1. temperatureCool the reaction mixture to 20-25° C.
  2. filtrationfilter through diatomaceous earth (50.6 g)
  3. washWash the filter cake with acetonitrile (2×50.6 mL)
  4. concentrationconcentrate the filtrate under reduced pressure
  5. temperatureAdd toluene (152 mL), active carbon (2.53 g) and heat the mixture to 60-70° C. for 1-2 hours
  6. temperatureCool the mixture to 25-35° C.
  7. filtrationfilter the reaction mixture over diatomaceous earth (50.6 g)
  8. washRinse the filter cake with toluene (17.0 mL)
  9. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-cc169377bb3f478a81708f38078e0c20
Source dataset
uspto-grants-2013_10
Patent number
US08569286B2

Reaction notes

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