Racemic (3aSR,6aSR)-6a-(5-Bromo-2-fluorophenyl)hexahydrofuro[3,4-c]isoxazole → Racemic ((3RS,4SR)-4-Amino-4-(5-bromo-2-fluorophenyl)tetrahydrofuran-3-yl)methanol

HRID 2060751Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2060751
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([C:8]23[CH2:15][O:14][CH2:13][CH:12]2[CH2:11][O:10][NH:9]3)[CH:7]=1>C(O)(=O)C.[Zn]>[NH2:9][C:8]1([C:6]2[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=2[F:16])[CH2:15][O:14][CH2:13][CH:12]1[CH2:11][OH:10]

Komponenten

4

Edukt 1

HCID 57475807Racemic (3aSR,6aSR)-6a-(5-Bromo-2-fluorophenyl)hexahydrofuro[3,4-c]isoxazole

Produkt 1

HCID 66847662Racemic ((3RS,4SR)-4-Amino-4-(5-bromo-2-fluorophenyl)tetrahydrofuran-3-yl)methanolAusbeute 86,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23994ZincKatalysatorHCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

Zinc powder (190 g, 2.91 mol) is added to a mixture of racemic (3aSR,6aSR)-6a-(5-bromo-2-fluorophenyl)hexahydrofuro[3,4-c]isoxazole (84 g, 290 mmol) in acetic acid (1.4 L) at a rate maintaining the temperature below 30° C. The reaction is heated at 40° C. for 5 h. The reaction is cooled to room temperature and is filtered through a pad of diatomaceous earth, washed with acetic acid and water (200 mL). The solvent is removed under reduced pressure. Water (500 mL) is added to the residue, and the pH is adjusted to pH 10 with 2 M aqueous sodium hydroxide. The basic aqueous suspension is extracted three times with 15% isopropyl alcohol in dichloromethane (3×500 mL). The combined organic layer is dried over magnesium sulfate and the solvent is removed under reduced pressure to give the title compound as a white solid (73.0 g, 86%). ES/MS m/e (79Br/81Br) 290, 292 (M+1).

Aufarbeitung

  1. temperaturemaintaining the temperature below 30° C
  2. temperatureThe reaction is cooled to room temperature
  3. filtrationis filtered through a pad of diatomaceous earth
  4. washwashed with acetic acid and water (200 mL)
  5. customThe solvent is removed under reduced pressure
  6. additionWater (500 mL) is added to the residue
  7. extractionThe basic aqueous suspension is extracted three times with 15% isopropyl alcohol in dichloromethane (3×500 mL)
  8. dry with materialThe combined organic layer is dried over magnesium sulfate
  9. customthe solvent is removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-af077f7407e8454b97b0f9ab0d2a5da9
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08278441B2

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