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

HRID 857461노트

반응식

HRID 857461 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 94433Tetrabutylammonium hydrogen sulfate촉매HCID 6342Acetonitrile용매

실험 절차

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).

후처리

  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)]

출처 및 근거

ORD 기록
ord-e99f1e026d8845acaedd70d6424a55dd
출처 데이터셋
uspto-grants-2006_12
특허 번호
US07145009B2

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