Dimethylformamide → 1H-Indol-1-amine, 6-(trifluoromethyl)-

HRID 2382065Notes

Reaction equation

HRID 2382065 reaction equation
[H-].[Na+].[F:3][C:4]([F:15])([F:14])[C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][NH:11]2)=[CH:7][CH:6]=1.C[N:17](C=O)C>>[F:15][C:4]([F:3])([F:14])[C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][N:11]2[NH2:17])=[CH:7][CH:6]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 27775236-(Trifluoromethyl)indole

Product 1

HCID 685531851H-Indol-1-amine, 6-(trifluoromethyl)-Yield 83%

Conditions

Temperature
0 °C

Procedure

A suspension of NaH (6.5 g, 162 mmol, 60% in mineral oil) in DMF (54 mL) at 0° C. is treated with 6-trifluoromethylindole (2.0 g, 10.8 mmol) and stirred at 0° C. for 0.5 h. The mixture is treated with HOSA (6.1 g, 54 mmol) portion wise and warmed to rt over 2 h. The mixture is then poured over ice and filtered through a pad of Celite. The filtrate is extracted with Et2O (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10%-30% EtOAc in heptane to afford 6-trifluoromethyl-indol-1-ylamine (1.79 g, 83%). MS: 201 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.74 (s, 1H), 7.67 (d, 1H), 7.35 (d, 1H), 7.30 (m, 1H), 6.45 (d, 1H), 4.83 (s, NH2, 2H).

Workup

  1. additionThe mixture is treated with HOSA (6.1 g, 54 mmol) portion wise
  2. temperaturewarmed to rt over 2 h
  3. additionThe mixture is then poured over ice
  4. filtrationfiltered through a pad of Celite
  5. extractionThe filtrate is extracted with Et2O (3×50 mL)
  6. dry with materialThe combined organic layer is dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by silica gel chromatography
  10. washeluting with 10%-30% EtOAc in heptane

Sources & evidence

ORD record
ord-480acb37191f4f45a8614909d6ef27f7
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

Loading…