Water → 7-chloro-5-fluoro-1H-indole

HRID 844201Notes

Reaction equation

HRID 844201 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:9]=[C:10]([F:19])[CH:11]=[C:12]2[C:16]=1[NH:15][C:14](=O)[C:13]2=O.O.[OH-].[Na+]>C1COCC1>[Cl:7][C:8]1[CH:9]=[C:10]([F:19])[CH:11]=[C:12]2[C:16]=1[NH:15][CH:14]=[CH:13]2

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 16793679HCID 16793679, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 226127407-chloro-5-fluoro-1H-indoleYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of lithium aluminium hydride (0.57 g, 15 mmol) in THF (20 mL) at 0° C. under Ar was added portionwise 7-chloro-5-fluoroindole-2,3-dione. The mixture was heated under reflux for 4 h, cooled to 0° C. and water (0.5 mL) was added. The mixture was stirred for 5 min then treated with aqueous sodium hydroxide solution (2 N, 0.5 mL) followed by water (0.5 mL) and filtered through a pad of celite®. The filter-cake was washed with tetrahydrofuran and the filtrate was concentrated in vacuo and purified by column chromatography [SiO2; heptane-ethyl acetate (3:1)] to give the product (0.31 g, 37% yield) as a blue-oil: IR νmax (film)/cm−1 3459, 1575, 1485, 1341, 1120 and 722; NMR δH (400 MHz, CDCl3) 6.55 (1H, t, J 2.5 Hz) 7.01 (1H, dd, J 9,2 Hz) 7.21 (1H, m) 7.29 (1H, t, J 2.5 Hz) 8.33 (1H, brs).

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 4 h
  3. filtrationfiltered through a pad of celite®
  4. washThe filter-cake was washed with tetrahydrofuran
  5. concentrationthe filtrate was concentrated in vacuo
  6. custompurified by column chromatography [SiO2; heptane-ethyl acetate (3:1)]

Sources & evidence

ORD record
ord-3df4ccd62cb84507a1e0dc365e74fb5e
Source dataset
uspto-grants-2002_04
Patent number
US06380238B1

Reaction notes

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