Aluminium lithium hydride → 7-bromo-3-methyl-5-(trifluoromethyl)-1H-indole

HRID 913962Notes

Reaction equation

HRID 913962 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Br:7][C:8]1[CH:9]=[C:10]([C:19]([F:22])([F:21])[F:20])[CH:11]=[C:12]2[C:16]=1[NH:15][CH:14]=[C:13]2[CH:17]=O>C1COCC1>[Br:7][C:8]1[CH:9]=[C:10]([C:19]([F:22])([F:20])[F:21])[CH:11]=[C:12]2[C:16]=1[NH:15][CH:14]=[C:13]2[CH3:17]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 575460277-bromo-5-(trifluoromethyl)-1H-indole-3-carbaldehyde

Product 1

HCID 575461317-bromo-3-methyl-5-(trifluoromethyl)-1H-indoleYield 57.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminum hydride (16.98 ml, 16.98 mmol) was added to a −40° C. solution of 7-bromo-5-(trifluoromethyl)-1H-indole-3-carbaldehyde (1.24 g, 4.25 mmol) in THF (10 ml). The reaction was stirred between −30° C and −10° C. for 40 min and was quenched with saturated aqueous ammonium chloride (1 mL) and filtered through celite and washed with ethyl acetate (20 mL). The filtrate was evaporated and the residue was purified by chromatography on SiO2 with a gradient of 4% to 30% ethyl acetate/hexanes. The product 7-bromo-3-methyl-5-(trifluoromethyl)-1H-indole (677 mg, 2.435 mmol, 57.3% yield) was obtained as a white solid. 1H-NMR (CDCl3, 400 MHz) δ 8.35 (s, 1H), 7.80(d, J=1.2 Hz, 1H), 7.57 (d, J=0.9 Hz, 1H), 7.12,(q, J=1.2 Hz, 1H), 2.33(d, J=1.2 Hz, 3H). LC (HPLC method 4): tR=3.45 min.

Workup

  1. customwas quenched with saturated aqueous ammonium chloride (1 mL)
  2. filtrationfiltered through celite
  3. washwashed with ethyl acetate (20 mL)
  4. customThe filtrate was evaporated
  5. customthe residue was purified by chromatography on SiO2 with a gradient of 4% to 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-fb0d8e20971a4927ac5db3fc09e2e391
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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