Water → 1-(6-Chloro-5-fluoroindol-1-yl)-2-ethylamine

HRID 857461Notes

Reaction equation

HRID 857461 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][C:5]=1[F:13].Cl.Cl[CH2:16][CH2:17][NH2:18].O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(#N)C>[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][N:10]2[CH2:16][CH2:17][NH2:18])=[CH:6][C:5]=1[F:13]

Participants

7

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 27736486-Chloro-5-fluoro-1H-indoleHCID 97937372-Chloroethylamine hydrochloride

Product 1

HCID 189862171-(6-Chloro-5-fluoroindol-1-yl)-2-ethylamineYield 80%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6342AcetonitrileSolvent

Procedure

Tetra-n-butylammonium hydrogensulfate (0.1 g, 0.33 mmol), powdered sodium hydroxide (1.3 g, 33 mmol) and 6-chloro-5-fluoroindole (1.4 g, 8.3 mmol) were stirred at room temperature in acetonitrile (40 mL) for 1 h. 2-Chloroethylamine hydrochloride (1.45 g, 12.5 mmol) was then added in 1 portion and the reaction was heated to reflux and stirred for 36 h. After allowing to cool to room temperature the mixture was poured into water (100 mL) and extracted with ethyl acetate (3×70 mL). The combined organic extracts were washed with brine (1×100 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude oil. The oil was purified by flash column chromatography [SiO2; ethyl acetate-methanol-ammonium hydroxide, (90:9:1)] to give the product as an orange oil (1.4 g, 80%). IR νmax (film)/cm−1 3377, 3104, 2937, 2868, 1675, 1568, 1505, 1479, 1449, 1400, 1357, 1327, 1291, 1236, 1143, 1090, 1030, 994, 862, 817, 753, 717, 698, 678, 646, 633, 596 and 579; NMR δH (400 MHz; DMSO-d6) 7.79 (1H, d, J 7 Hz), 7.51 (1H, d, J 10 Hz), 7.50 (1H, d, J 3.5 Hz), 6.46 (1H, m), 4.13 (2H, t, J 6.3 Hz), 2.86 (2H, t, J 6.3 Hz), 1.52 (1H, br. s).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux
  3. extractionextracted with ethyl acetate (3×70 mL)
  4. washThe combined organic extracts were washed with brine (1×100 mL)
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. customthe solvent removed under vacuum
  8. customto leave a crude oil
  9. customThe oil was purified by flash column chromatography [SiO2; ethyl acetate-methanol-ammonium hydroxide, (90:9:1)]

Sources & evidence

ORD record
ord-e99f1e026d8845acaedd70d6424a55dd
Source dataset
uspto-grants-2006_12
Patent number
US07145009B2

Reaction notes

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