Hydroxyamine hydrochloride → 1-Azabicyclo[3.2.1]octan-3-amine

HRID 1072974ノート

反応式

HRID 1072974 の反応式
Cl.[N:2]12[CH2:9][C@H:6]([CH2:7][CH2:8]1)[CH2:5][C:4](=O)[CH2:3]2.Cl.[NH2:12]O.O.O.O.C([O-])(=O)C.[Na+].[Na]>CS(C)=O.C(O)C>[N:2]12[CH2:9][CH:6]([CH2:7][CH2:8]1)[CH2:5][CH:4]([NH2:12])[CH2:3]2

参加物

7

反応物 4

HCID 443297Hydroxyamine hydrochlorideHCID 5360545SodiumHCID 23665404Sodium Acetate TrihydrateHCID 24774188HCID 24774188、化合物

生成物 1

HCID 207565511-Azabicyclo[3.2.1]octan-3-amine

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 702Ethanol溶媒

反応条件

温度
100 °C

実験手順

To a flask containing (5R)-1-azabicyclo[3.2.1]octan-3-one hydrochloride (3.64 g, 22.6 mmol), hydroxylamine hydrochloride (2.04 g, 29.4 mmol), and ethanol (130 mL) is added sodium acetate trihydrate (9.23 g, 67.8 mmol). The mixture stirred for 3 h and is filtered and concentrated. The resulting white solid is taken up in n-propanol (100 mL) and sodium (˜13.6 g, 618 mmol) is added in 20-25 portions. The reaction spontaneously begins to reflux, and the reaction is heated in an oil bath (100° C.). The addition is complete in ˜20 min and the mixture solidifies after ˜40 min. The oil bath is removed and n-propanol (2×25 mL) is added dissolving the remaining sodium metal. The mixture is carefully quenched through the dropwise addition of H2O (100 mL). Saturated aq. NaCl (20 mL) is added, and the layers are separated. The organic layer is dried (MgSO4), filtered, treated with freshly prepared MeOH/HCl, and concentrated. The resulting solid is triturated with 30 mL EtOH, filtered and dried in vaccuo to afford 3.51 g as a white solid: [α]25D=−3 (c 0.94, DMSO); 1H NMR (400 MHz, DMSO-d6) δ 3.60-3.80, 2.95-3.10, 2.65-2.75, 1.90-2.15, 1.70-1.90; HRMS (FAB) calcd for C7H14N2 (M+H+) 127.1235, found 127.1235.

後処理

  1. filtrationis filtered
  2. concentrationconcentrated
  3. customThe reaction
  4. temperatureto reflux
  5. additionThe addition
  6. waitis complete in ˜20 min
  7. waitthe mixture solidifies after ˜40 min
  8. customThe oil bath is removed
  9. additionn-propanol (2×25 mL) is added
  10. dissolutiondissolving the remaining sodium metal
  11. customThe mixture is carefully quenched through the dropwise addition of H2O (100 mL)
  12. additionSaturated aq. NaCl (20 mL) is added
  13. customthe layers are separated
  14. dry with materialThe organic layer is dried (MgSO4)
  15. filtrationfiltered
  16. additiontreated with freshly prepared MeOH/HCl
  17. concentrationconcentrated
  18. customThe resulting solid is triturated with 30 mL EtOH
  19. filtrationfiltered
  20. customdried in vaccuo
  21. customto afford 3.51 g as a white solid

出典と根拠

ORDレコード
ord-e71ddbdff34f4bd488f1142a6402b9ed
出典データセット
uspto-grants-2005_06
特許番号
US06911543B2

反応ノート

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