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

HRID 1045785Notes

Reaction equation

HRID 1045785 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:8][CH2:9][O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].[CH:18]1[C:28]2[C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[CH2:25][C:24](=[O:33])[NH:23][C:22]=2[N:21]=[CH:20][CH:19]=1.O>CN(C)C=O.[I-].[Na+].C(OCC)(=O)C>[Si:11]([O:10][CH2:9][CH2:8][N:23]1[C:22]2[N:21]=[CH:20][CH:19]=[CH:18][C:28]=2[C:27]2[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=2[CH2:25][C:24]1=[O:33])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]

Participants

8

Reactant 4

HCID 962WaterHCID 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-oneYield 102.8%

Reagents, catalysts & solvents 3

HCID 5238Sodium IodideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Add cesium carbonate (186.6 g, 572.7 mmol), (2-bromoethoxy)-tert-butyldimethylsilane (88.0 mL, 409.1 mmol), and sodium iodide (6.1 g, 40.9 mmol) to a suspension of 5,7-dihydropyrido[2,3-d][3]benzazepin-6-one (86.0 g, 409.1 mmol) in dimethylformamide (860 mL) and stir at 70° C. for 20 hours. Cool mixture to ambient temperature, pour over ice and water (100 mL), add ethyl acetate (200 mL). Filter mixture through Celite®, then wash with ethyl acetate (100 mL). Separate layers of filtrate, extract from aqueous with ethyl acetate (2×50 mL). Wash combined organics with water (2×100 mL), brine (100 mL), dry over sodium sulfate and concentrate. Dissolve material in tetrahydrofuran (1.28 L), add Silia® bond palladium scavenger (16.7 g) and stir at ambient temperature for 20 hours. Filter through a pad of silica, wash with tetrahydrofuran (200 mL) and concentrate to obtain the title compound (155 g, 420.6 mmol) as a light brown oil that crystallizes in quantitative yield. MS (m/z): 369 (M+1).

Workup

  1. temperatureCool mixture to ambient temperature
  2. filtrationFilter mixture through Celite®
  3. washwash with ethyl acetate (100 mL)
  4. extractionSeparate layers of filtrate, extract from aqueous with ethyl acetate (2×50 mL)
  5. washWash
  6. dry with materialdry over sodium sulfate
  7. concentrationconcentrate
  8. additionDissolve material in tetrahydrofuran (1.28 L), add Silia® bond palladium scavenger (16.7 g)
  9. stirringstir at ambient temperature for 20 hours
  10. filtrationFilter through a pad of silica
  11. washwash with tetrahydrofuran (200 mL)
  12. concentrationconcentrate

Sources & evidence

ORD record
ord-31ba4aaa5ed342339ee12283d9859f34
Source dataset
uspto-grants-2013_10
Patent number
US08569286B2

Reaction notes

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