Toluene → HCID 86676259, compound

HRID 1045795Notes

Reaction equation

HRID 1045795 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][N:11]1[C:17]2[N:18]=[CH:19][CH:20]=[CH:21][C:16]=2[C:15]2[CH:22]=[CH:23][CH:24]=[CH:25][C:14]=2[CH2:13][C:12]1=[O:26])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1(C)C=CC=CC=1.CC(C)([O-])C.[K+].[N:40](OCCC(C)C)=[O:41]>O.C(OCC)(=O)C>[Si:1]([O:8][CH2:9][CH2:10][N:11]1[C:17]2[N:18]=[CH:19][CH:20]=[CH:21][C:16]=2[C:15]2[CH:22]=[CH:23][CH:24]=[CH:25][C:14]=2[C:13](=[N:40][OH:41])[C:12]1=[O:26])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 1140TolueneHCID 8053Isoamyl NitriteHCID 23665647Potassium tert-butoxideHCID 712371035-[2-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]ethyl]-5,7-dihydro-6H-pyrido[3,2-a][3]benzazepin-6-one

Product 1

HCID 86676259HCID 86676259, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

Combine 5-[2-(tert-butyl(dimethyl)silyl)oxyethyl]-7H-pyrido[2,3-d][3]benzazepin-6-one (30.0 g, 0.08 mol) and toluene (300.0 mL), cool the reaction mixture to −10-0° C. Add potassium tert-butoxide (18.2 g, 0.16 mol), isoamyl nitrite (13.34 g, 0.11 mol) and then stir for 3-5 hours. Transfer the reaction mixture to a cool (0-5° C.) biphasic solution of ethyl acetate (210 mL) and water (510 mL) and stir for 15-30 minutes. Warm the reaction mixture to 15-25° C. and separate the layers. Extract the aqueous layer with additional ethyl acetate (120 mL) and methyl tert-butyl ether (120 mL) and combine the organic layers. Concentrate the organic under reduced pressure to a solution volume of approximately 60-90 mL and then add toluene (240 mL) and ethyl acetate (75 mL). Filter the solution through silica gel (45.0 g), rinse the silica gel with a mixture of toluene (210 mL) and ethyl acetate (60 mL), and concentrate the filtrate under reduced pressure to a volume of approximately 75 mL. Add heptane (120 mL) and concentrate the mixture to a volume of approximately 60 mL and filter the resulting solids. Wash the filter cake with heptane (25 mL) and dry under vacuum to provide the title compound (28.3 g, 72.5%) as a yellow solid.

Workup

  1. customseparate the layers
  2. extractionExtract the aqueous layer with additional ethyl acetate (120 mL) and methyl tert-butyl ether (120 mL)
  3. concentrationConcentrate the organic under reduced pressure to a solution volume of approximately 60-90 mL
  4. filtrationFilter the solution through silica gel (45.0 g)
  5. washrinse the silica gel
  6. additionwith a mixture of toluene (210 mL) and ethyl acetate (60 mL)
  7. concentrationconcentrate the filtrate under reduced pressure to a volume of approximately 75 mL
  8. concentrationAdd heptane (120 mL) and concentrate the mixture to a volume of approximately 60 mL
  9. filtrationfilter the resulting solids
  10. washWash the filter cake with heptane (25 mL)
  11. customdry under vacuum

Sources & evidence

ORD record
ord-f8a8d232b07a460fac763c40ff1763c1
Source dataset
uspto-grants-2013_10
Patent number
US08569286B2

Reaction notes

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