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

HRID 1045786Notes

Reaction equation

HRID 1045786 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]>CN(C)C=O>[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-oneYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

Heat a mixture 5,7-dihydropyrido[2,3-d][3]benzazepin-6-one (22.5 g, 106.9 mmol) and dimethylformamide (500 mL) to 100° C. for 5 minutes. Cool to 40° C., add cesium carbonate (104.3 g, 320.1 mmol) and (2-bromoethoxy)-tert-butyldimethylsilane (29.9 mL, 138.9 mmol) and stir at ambient temperature overnight. Heat to 60° C. for approximately 2 hours, and then cool to ambient temperature. Partition the residue between ethyl acetate (1 L) and water (3 L), back extract from aqueous layer with ethyl acetate (2×500 mL), wash combined organics with brine (2×500 mL). Dry combined organics over sodium sulfate and concentrate. Purify the residue by flash chromatography, eluting with ethyl acetate:hexane (0:100 to 100:0) to give the title compound as an oil (39.4 g, 106.9 mmol, 89%). MS (m/z): 369 (M+1).

Workup

  1. temperatureHeat to 60° C. for approximately 2 hours
  2. temperaturecool to ambient temperature
  3. customPartition the residue between ethyl acetate (1 L) and water (3 L)
  4. extractionback extract from aqueous layer with ethyl acetate (2×500 mL)
  5. washwash
  6. customDry
  7. concentrationconcentrate
  8. customPurify the residue by flash chromatography
  9. washeluting with ethyl acetate:hexane (0:100 to 100:0)

Sources & evidence

ORD record
ord-a680b9abc4df433aa3518520ef5bdc9d
Source dataset
uspto-grants-2013_10
Patent number
US08569286B2

Reaction notes

Loading…