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

HRID 1252566

반응식

HRID 1252566 반응식
[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]

참가 물질

10

반응물 7

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

생성물 1

HCID 147716532-Fluoromethyl-2-amino-5-benzyloxypentanenitrile수율 55,538%

시약·촉매·용매 2

HCID 962Water용매HCID 3283Diethyl Ether용매4회

반응 조건

온도
-40 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2376f4fb4bb143f59cef7eca81b9c24e
출처 데이터셋
uspto-grants-1988_05
특허 번호
US04743691

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