Trifluoroacetic acid → HCID 67404804, compound

HRID 913430Notes

Reaction equation

HRID 913430 reaction equation
[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH:13]([F:15])[F:14])[NH:6]2.[BH3-]C#N.[Na+].[C:20](O)([C:22]([F:25])([F:24])[F:23])=O>>[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]([CH:13]([F:14])[F:15])[N:6]2[CH2:20][C:22]([F:25])([F:24])[F:23].[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]([CH:13]([F:14])[F:15])[NH:6]2

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydride2×HCID 249856324-chloro-2-(difluoromethyl)-1H-indole-5-carbonitrile

Product 2

HCID 24983830HCID 24983830, compoundYield 29%HCID 67404804HCID 67404804, compoundYield 40%

Procedure

To an ice-cold suspension of 4-chloro-2-(difluoromethyl)-1H-indole-5-carbonitrile (0.010 g, 0.044 mmol) in TFA (1 mL) was added NaCNBH3 (0.028 g, 0.44 mmol) in portions. After 10 min, the cold bath was removed and the mixture stirred at rt. After 1.5 h, additional NaCNBH3 (0.014 g, 0.22 mmol) was added and the mixture was stirred at rt another 20 min. The mixture was concentrated to dryness in in vacuo at 45° C. The residue was partitioned between EtOAc and 0.2N NaOH. The organic phase was washed with a sat'd NaHCO3 solution and brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by radial chromatography (10-100% CH2Cl2-hexanes) to afford 4-chloro-2-(difluoromethyl)-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-indole-5-carbonitrile (0.004 g, 29% yield) (MS (ES) m/z 311 (M+1)) and 4-chloro-2-(difluoromethyl)-2,3-dihydro-1H-indole-5-carbonitrile (0.004 g, 40% yield) (MS (ES) m/z 229 (M+1)).

Workup

  1. customthe cold bath was removed
  2. waitAfter 1.5 h
  3. stirringthe mixture was stirred at rt another 20 min
  4. concentrationThe mixture was concentrated to dryness in in vacuo at 45° C
  5. customThe residue was partitioned between EtOAc and 0.2N NaOH
  6. washThe organic phase was washed with a sat'd NaHCO3 solution and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by radial chromatography (10-100% CH2Cl2-hexanes)

Sources & evidence

ORD record
ord-a7d7418b7fa44dedb172b2bbd0e0aace
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

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