Potassium Carbonate → (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide

HRID 606730ノート

反応式

HRID 606730 の反応式
Cl.[NH2:2][C:3]12[CH2:10][CH2:9][C:6]([C:11]([O:13][CH2:14][CH3:15])=[O:12])([CH2:7][CH2:8]1)[CH2:5][CH2:4]2.C(=O)([O-])[O-].[K+].[K+].C1(S(O[CH2:32][C:33]([N:35]2[CH2:39][C@@H:38]([F:40])[CH2:37][C@H:36]2[C:41]([NH2:43])=[O:42])=[O:34])(=O)=O)C=CC=CC=1>CN(C)C=O>[CH2:14]([O:13][C:11]([C:6]12[CH2:5][CH2:4][C:3]([NH:2][CH2:32][C:33]([N:35]3[CH2:39][C@@H:38]([F:40])[CH2:37][C@H:36]3[C:41]([NH2:43])=[O:42])=[O:34])([CH2:10][CH2:9]1)[CH2:8][CH2:7]2)=[O:12])[CH3:15]

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 24781877(2S,4S)-1-[2-(benzenesulfonyloxy)acetyl]-4-fluoropyrrolidine-2-carboxamideHCID 66790102Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrochloride

生成物 1

HCID 46854534(2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide収率 45%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
45 °C

実験手順

Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrochloride (4.63 g), potassium carbonate (5.47 g) and N,N-dimethylformamide (40 mL) were mixed together. To this mixture, a solution of (2S,4S)-1-[2-(benzenesulfonyloxy)acetyl]-4-fluoropyrrolidine-2-carboxamide (5.93 g) in N,N-dimethylformamide (10 mL) was added at 40° C. and the mixture was stirred at 45° C. for 3 hours. Subsequently, the reaction mixture was concentrated under reduced pressure. Water (50 mL) was then added to the residue and the resulting crystal was collected by filtration, washed with water (30 mL), and dried at 50° C. under reduced pressure. The crude crystal was recrystallized from ethyl acetate (40 mL), washed with ethyl acetate (20 mL), and dried at room temperature under reduced pressure. This gave (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]ac etyl]-4-fluoropyrrolidine-2-carboxamide as a white solid in the form of colorless powder (1.81 g). The filtrate and the wash were combined and concentrated to 20 mL. The resulting crystal was collected by filtration, washed with a mixture of ethyl acetate and diisopropyl ether (1:1, 20 mL) to give additional 1.19 g of the product. The total amount of the product was 3.00 g (45% yield).

後処理

  1. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
  2. additionWater (50 mL) was then added to the residue
  3. filtrationthe resulting crystal was collected by filtration
  4. washwashed with water (30 mL)
  5. customdried at 50° C. under reduced pressure
  6. customThe crude crystal was recrystallized from ethyl acetate (40 mL)
  7. washwashed with ethyl acetate (20 mL)
  8. customdried at room temperature under reduced pressure
  9. concentrationconcentrated to 20 mL
  10. filtrationThe resulting crystal was collected by filtration
  11. washwashed with a mixture of ethyl acetate and diisopropyl ether (1:1, 20 mL)

出典と根拠

ORDレコード
ord-69804196597545e5844e44d3ef2a0462
出典データセット
uspto-grants-2011_03
特許番号
US07915427B2

反応ノート

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