Sodium Chloride → 2-Fluoromethyl-2-amino-5-benzyloxypentanenitrile

HRID 1252566ノート

反応式

HRID 1252566 の反応式
[Mg].CI.Cl[CH2:5][CH2:6][CH2:7][O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[F:16][CH2:17][C:18]#[N:19].[C-:20]#[N:21].[Na+].[Cl-].[NH4+].[Cl-].[Na+]>CCOCC.O>[F:16][CH2:17][C:18]([NH2:19])([CH2:5][CH2:6][CH2:7][O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:20]#[N:21]

参加物

10

反応物 7

HCID 5234Sodium ChlorideHCID 6328Methyl iodideHCID 8929Sodium CyanideHCID 10420Acetonitrile, fluoro-HCID 25517Ammonium ChlorideHCID 221505((3-Chloropropoxy)methyl)benzeneHCID 5462224Magnesium

生成物 1

HCID 147716532-Fluoromethyl-2-amino-5-benzyloxypentanenitrile収率 55,538%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 3283Diethyl Ether溶媒4 回

反応条件

温度
-40 °C

実験手順

To magnesium turnings (30.6 g, 1.26 mol), suspended in dry ether (150 ml) is added methyl iodide (~ 0.5 ml) and then a solution of 1-chloro-3-benzyloxypropane (116 g, 0.63 mol) in ether (1.1l) at such a rate that gentle reflux is maintained. This procedure is performed under nitrogen. After the mixture is heated for 1 more hour under reflux, titration indicates Grignard formation to be complete. The solution is separated from the excess of magnesium (glass wool), transfered to a 6 l flask and, again under nitrogen, cooled to -40° C. Fluoroacetonitrile (33.48 g, 0.57 mmol) in ether (300 ml) is added slowly. The mixture is then kept at -40° C. for another 1/2 hour and is poured into a mixture of sodium cyanide (123 g), ammonium chloride (186 g), ice (600 g), and water (650 ml). The mixture is stirred vigorously and allowed to warm up to room temperature during 1 hour. Ether is added, the aqueous phase is saturated with sodium chloride, and the organic layer is separated. The aminonitrile is extracted with 1N HCl (2×750 ml) and re-extracted with ether (2×750 ml) after basification with concentrated ammonia. Drying (Na2SO4) and evaporation gives 2-fluoromethyl-2-amino-5-benzyloxypentanenitrile as a brown oil (74.8 g).

後処理

  1. temperatureis maintained
  2. temperatureAfter the mixture is heated for 1 more hour
  3. temperatureunder reflux
  4. customThe solution is separated from the excess of magnesium (glass wool)
  5. customtransfered to a 6 l flask and, again under nitrogen
  6. temperatureto warm up to room temperature during 1 hour
  7. customthe organic layer is separated
  8. extractionThe aminonitrile is extracted with 1N HCl (2×750 ml)
  9. extractionre-extracted with ether (2×750 ml) after basification with concentrated ammonia
  10. customDrying
  11. custom(Na2SO4) and evaporation

出典と根拠

ORDレコード
ord-2376f4fb4bb143f59cef7eca81b9c24e
出典データセット
uspto-grants-1988_05
特許番号
US04743691

反応ノート

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