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 2060751ノート

反応式

HRID 2060751 の反応式
[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]

参加物

4

反応物 1

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

生成物 1

HCID 66847662Racemic ((3RS,4SR)-4-Amino-4-(5-bromo-2-fluorophenyl)tetrahydrofuran-3-yl)methanol収率 86.8%

試薬・触媒・溶媒 2

HCID 23994Zinc触媒HCID 176Acetic Acid溶媒

反応条件

温度
40 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-af077f7407e8454b97b0f9ab0d2a5da9
出典データセット
uspto-grants-2012_10
特許番号
US08278441B2

反応ノート

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