Lithium borohydride → 1-(1-hydroxypropan-2-yl)-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 1851103

Reaktionsgleichung

Reaktionsgleichung von HRID 1851103
[C:1]([C:3]1[C:4]([C:19]([F:22])([F:21])[F:20])=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH:12]([CH3:17])[C:13](OC)=[O:14])[C:7]([CH3:18])=[CH:6]2)#[N:2].[Li+].[BH4-]>C1COCC1>[OH:14][CH2:13][CH:12]([N:8]1[C:9]2[C:5](=[C:4]([C:19]([F:22])([F:20])[F:21])[C:3]([C:1]#[N:2])=[CH:11][CH:10]=2)[CH:6]=[C:7]1[CH3:18])[CH3:17]

Komponenten

4

Edukt 2

HCID 4148881Lithium borohydrideHCID 57800182Methyl 2-[5-cyano-2-methyl-4-(trifluoromethyl)-1H-indol-1-yl]propanoate

Produkt 1

HCID 772853621-(1-hydroxypropan-2-yl)-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrileAusbeute 88,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To an ice-cold solution of methyl 2-(5-cyano-2-methyl-4-(trifluoromethyl)-1H-indol-1-yl)propanoate (Example 1) (0.263 g, 0.848 mmol) in THF (5 mL) was added dropwise LiBH4 (2M in THF) (1.695 mL, 3.39 mmol). After complete addition of the reducing agent, the cold bath was removed and the mixture was stirred at rt. After 2 h, the reaction mixture was cooled in an ice bath and a saturated aqueous NH4Cl solution (15 mL) was added slowly. The mixture was then diluted with EtOAc (40 mL) and treated slowly with 1N HCl (10 mL). The phases were separated and the aqueous phase was washed with EtOAc (20 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was chromatographed over silica gel using a 20-60% EtOAc-hexane gradient to give 1-(1-hydroxypropan-2-yl)-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (0.212 g, 83% yield) as a white solid: MS (ESI): m/z 283 (MH+).

Aufarbeitung

  1. additionAfter complete addition of the reducing agent
  2. customthe cold bath was removed
  3. temperaturethe reaction mixture was cooled in an ice bath
  4. additiona saturated aqueous NH4Cl solution (15 mL) was added slowly
  5. additionThe mixture was then diluted with EtOAc (40 mL)
  6. additiontreated slowly with 1N HCl (10 mL)
  7. customThe phases were separated
  8. washthe aqueous phase was washed with EtOAc (20 mL)
  9. washThe combined organic phases were washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was chromatographed over silica gel using a 20-60% EtOAc-hexane gradient

Quellen und Nachweise

ORD-Eintrag
ord-15ca5b39f8cd40fa8a674981613ed86a
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08957104B2

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