1,1'-Carbonyldiimidazole → (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amide

HRID 1516624ノート

反応式

HRID 1516624 の反応式
C(N1C=CN=C1)([N:3]1C=CN=C1)=O.[F:13][C:14]1[CH:15]=[C:16]([CH:34]=[CH:35][CH:36]=1)[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29](=[O:30])[CH2:28][C@H:27]([C:31](O)=[O:32])[CH2:26]2)=[CH:21][CH:20]=1>O1CCCC1>[F:13][C:14]1[CH:15]=[C:16]([CH:34]=[CH:35][CH:36]=1)[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29](=[O:30])[CH2:28][C@H:27]([C:31]([NH2:3])=[O:32])[CH2:26]2)=[CH:21][CH:20]=1

参加物

4

反応物 2

HCID 682631,1'-CarbonyldiimidazoleHCID 67409315(S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid

生成物 1

HCID 44128415(S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amide収率 96.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
18 °C

実験手順

1,1′-carbonyldiimidazole (8.27 g, 51.0 mmol) was suspended and partly dissolved in tetrahydrofuran (110 mL) at 18° C. (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (14.0 g, 42.5 mmol; enantiomeric purity (S):(R)=99.5:0.5) was added as a solid together with tetrahydrofuran (30 mL) used for rinsing. The turbid solution, which turned into a white suspension after 15 min, was stirred 1 h at 16-20° C. and then transferred into a stirred 25% aqueous ammonia solution (7.95 mL) in tetrahydrofuran (80 mL). The last part of the white suspension was transferred with the aid of tetrahydrofuran (10 mL) for rinsing. After stirring for 0.5 h the reaction mixture was concentrated in vacuo to a volume of ˜70 mL and diluted with water (300 mL). Some ice was added to keep the temperature at 20-25° C. The white precipitate was collected by filtration, washed with water/tetrahydrofuran 80:20 and with heptane. Drying in vacuo at 20-45° C. afforded (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amide (13.5 g, 96%) as a white solid. The purity of the material by HPLC was 96.9% (area) and the enantiomeric ratio (S):(R) was determined as 99.7:0.3.

後処理

  1. washfor rinsing
  2. washfor rinsing
  3. stirringAfter stirring for 0.5 h the reaction mixture
  4. concentrationwas concentrated in vacuo to a volume of ˜70 mL
  5. additiondiluted with water (300 mL)
  6. additionSome ice was added
  7. customat 20-25° C
  8. filtrationThe white precipitate was collected by filtration
  9. washwashed with water/tetrahydrofuran 80:20 and with heptane
  10. customDrying in vacuo at 20-45° C.

出典と根拠

ORDレコード
ord-cdbd61a6a0ad400e92a51b2194a13bf3
出典データセット
uspto-grants-2012_07
特許番号
US08227505B2

反応ノート

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