Hydrochloric Acid → trans-1-[2-(4-Fluorophenyl)-ethyl]-4-ethylpiperidin-3-ylmethylamine

HRID 896566ノート

反応式

HRID 896566 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[C:15](=O)[CH2:14][CH:13]([CH2:17][CH3:18])[CH:12]([C:19]#[N:20])[C:11]2=O)=[CH:4][CH:3]=1.B.O1CCCC1.Cl>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][C@@H:13]([CH2:17][CH3:18])[C@H:12]([CH2:19][NH2:20])[CH2:11]2)=[CH:4][CH:3]=1

参加物

5

反応物 4

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 8028TetrahydrofuranHCID 223502401-[2-(4-Fluorophenyl)ethyl]-4-ethyl-2,6-dioxopiperidine-3-carbonitrile

生成物 1

HCID 69737962trans-1-[2-(4-Fluorophenyl)-ethyl]-4-ethylpiperidin-3-ylmethylamine収率 37.1%

実験手順

1-[2-(4-Fluorophenyl)ethyl]-4-ethyl-2,6-dioxopiperidine-3-carbonitrile (1.0 g, 3.47 mmol) was treated with 1.0 M borane in tetrahydrofuran (69.4 mL, 69.4 mmol) and stirred at room temperature for 65 hours. The solution was cooled on an ice bath and treated very slowly with 2.0 N hydrochloric acid. The mixture was concentrated under vacuum to remove the tetrahydrofuran, and the aqueous residue was heated at reflux for 60 minutes. The mixture was cooled to room temperature and treated with 50% aqueous sodium hydroxide to adjust the pH to about 11. The mixture was extracted with ethyl acetate, and the organic extracts were dried over sodium sulfate and concentrated. The residue was purified by flash chromatography, eluting with 5% methanol in dichloromethane containing 0.5% aqueous ammonia, to provide an oil (340 mg, 37%). 1H NMR (300 MHz, CDCl3) δ7.16 (m, 2H), 6.97 (t, J=9 Hz, 2H), 3.13 (m, 1H), 3.00 (m, 1H), 2.92 (dd, J=13, 3 Hz, 1H), 2.83 (m, 2H), 2.58 (m, 2H), 1.99 (td, J=12, 3 Hz, 1H), 1.9-1.0 (m, 8H), 0.90 (t, J=7 Hz, 3H). Mass spec (ES+) m/z 265.4 (M+H+, 100%).

後処理

  1. temperatureThe solution was cooled on an ice bath
  2. concentrationThe mixture was concentrated under vacuum
  3. customto remove the tetrahydrofuran
  4. temperaturethe aqueous residue was heated
  5. temperatureat reflux for 60 minutes
  6. temperatureThe mixture was cooled to room temperature
  7. additiontreated with 50% aqueous sodium hydroxide
  8. extractionThe mixture was extracted with ethyl acetate
  9. dry with materialthe organic extracts were dried over sodium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography
  12. washeluting with 5% methanol in dichloromethane containing 0.5% aqueous ammonia

出典と根拠

ORDレコード
ord-f6eceaf89f614f7ea2fc15111b89a6ef
出典データセット
uspto-grants-2005_07
特許番号
US06919356B2

反応ノート

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