Diethyl Ether → 2-methyl-1-(1-methyl-2-oxopropyl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 1851102Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1851102
[CH3:1][Mg]I.[C:4]([C:6]1[C:7]([C:22]([F:25])([F:24])[F:23])=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH:15]([CH3:20])[C:16](OC)=[O:17])[C:10]([CH3:21])=[CH:9]2)#[N:5].[NH4+].[Cl-].[CH3:28]C[O:30][CH2:31][CH3:32]>CCOC(C)=O>[CH3:21][C:10]1[N:11]([CH:15]([CH3:20])[C:16](=[O:17])[CH3:28])[C:12]2[C:8]([CH:9]=1)=[C:7]([C:22]([F:25])([F:24])[F:23])[C:6]([C:4]#[N:5])=[CH:14][CH:13]=2.[OH:30][C:31]([CH3:32])([CH3:1])[CH:15]([N:11]1[C:12]2[C:8](=[C:7]([C:22]([F:24])([F:23])[F:25])[C:6]([C:4]#[N:5])=[CH:14][CH:13]=2)[CH:9]=[C:10]1[CH3:21])[CH3:16]

Komponenten

7

Edukt 4

HCID 3283Diethyl Ether2×HCID 25517Ammonium ChlorideHCID 57800182Methyl 2-[5-cyano-2-methyl-4-(trifluoromethyl)-1H-indol-1-yl]propanoateHCID 178418373HCID 178418373, Verbindung

Produkt 2

HCID 867091592-methyl-1-(1-methyl-2-oxopropyl)-4-(trifluoromethyl)-1H-indole-5-carbonitrileHCID 867091601-(2-hydroxy-1,2-dimethylpropyl)-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To an ice-cold solution of methyl magnesium iodide (3M in Et2O) (0.322 ml, 0.967 mmol) in Et2O (1 mL) was added a solution of methyl 2-[5-cyano-2-methyl-4-(trifluoromethyl)-1H-indol-1-yl]propanoate (Example 1) (0.100 g, 0.322 mmol) in Et2O (1 mL). The heterogeneous mixture was stirred in an ice bath for 5 min, at rt for 10 min, and then at 38° C. for ˜1 h. Upon cooling, the reaction mixture was diluted with EtOAc (5 mL) and treated with aq. saturated NH4Cl (5 mL). The mixture was partitioned between EtOAc (25 mL) and water (15 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was chromatographed over silica gel eluting sequentially with 50%, 75% and 100% CH2Cl2-hexanes to give 2-methyl-1-(1-methyl-2-oxopropyl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile (0.008 g, 8% yield, less polar product) (MS (ESI): m/z 295 (MH+)) and 1-(2-hydroxy-1,2-dimethylpropyl)-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (0.069 g, 60% yield, more polar product) (MS (ESI): m/z 311 (MH+).

Aufarbeitung

  1. waitat 38° C. for ˜1 h
  2. temperatureUpon cooling
  3. customThe mixture was partitioned between EtOAc (25 mL) and water (15 mL)
  4. washThe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed over silica gel eluting sequentially with 50%, 75% and 100% CH2Cl2-hexanes

Quellen und Nachweise

ORD-Eintrag
ord-b93393e5da5e4e9cac0313ca5cb04d9c
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08957104B2

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