4-Nitrobenzoyl chloride → (2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)pyrrolidine-1-carboxylate

HRID 403412

反応式

HRID 403412 の反応式
[CH2:1]([O:3][C:4]([C@@:6]1([NH:11][C:12]([C@@H:14]2[CH2:18][C@@H:17]([OH:19])[CH2:16][N:15]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:13])[CH2:8][C@H:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2].C(N(C(C)C)CC)(C)C.[N+:36]([C:39]1[CH:47]=[CH:46][C:42]([C:43](Cl)=[O:44])=[CH:41][CH:40]=1)([O-:38])=[O:37]>CN(C)C1C=CN=CC=1.CCOC(C)=O>[CH2:1]([O:3][C:4]([C@@:6]1([NH:11][C:12]([C@@H:14]2[CH2:18][C@@H:17]([O:19][C:43](=[O:44])[C:42]3[CH:41]=[CH:40][C:39]([N+:36]([O-:38])=[O:37])=[CH:47][CH:46]=3)[CH2:16][N:15]2[C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])=[O:13])[CH2:8][C@H:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2]

参加物

6

反応物 3

HCID 85024-Nitrobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 57892908(2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

生成物 1

HCID 59165437(2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)pyrrolidine-1-carboxylate

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
5 °C

実験手順

To a stirring slurry of (2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate (1.69 kg), 4-dimethylaminopyridine (28.0 g), diisopropylethylamine (946 g) and EtOAc (4.82 kg), at 10° C., was added p-nitrobenzoyl chloride (1.06 kg) as a solution in EtOAc (3.48 kg). After 2.5 h at 10° C., the reaction was cooled to 5° C. and quench by the addition of water (1.85 kg). The resulting layers were separated and the organic layer was washed with a 1.0 N aqueous solution of HCl (3.75 kg), 10% aqueous solution of KHCO3 (2×2.8 kg), water (3.1 kg), and a 10% aqueous solution of NaCl (3.1 kg). The organic layer was washed again with a 1.0 N aqueous solution of HCl (1.88 kg), 10% aqueous solution of KHCO3 (4.2 kg), H2O (1.5 kg), and a 10% aqueous solution of NaCl (2×755 g). The organic layer was concentrated under reduced pressure, diluted with EtOAc (5.6 kg), and then concentrated again. The resulting oil was diluted with EtOAc (10.0 kg), filtered, and then concentrated. EtOAc (10.0 kg) was added and then the resulting solution was concentrated to a mass of 7.9 kg. The assay yield was determined on the product-containing solution to be 98%.

後処理

  1. customquench by the addition of water (1.85 kg)
  2. customThe resulting layers were separated
  3. washthe organic layer was washed with a 1.0 N aqueous solution of HCl (3.75 kg), 10% aqueous solution of KHCO3 (2×2.8 kg), water (3.1 kg)
  4. washThe organic layer was washed again with a 1.0 N aqueous solution of HCl (1.88 kg), 10% aqueous solution of KHCO3 (4.2 kg), H2O (1.5 kg)
  5. concentrationThe organic layer was concentrated under reduced pressure
  6. additiondiluted with EtOAc (5.6 kg)
  7. concentrationconcentrated again
  8. additionThe resulting oil was diluted with EtOAc (10.0 kg)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. additionEtOAc (10.0 kg) was added
  12. concentrationthe resulting solution was concentrated to a mass of 7.9 kg
  13. customThe assay yield

出典と根拠

ORDレコード
ord-bfe975cdba4a463484dcb7b4abb4c63a
出典データセット
uspto-grants-2014_06
特許番号
US08748374B2

関連ノート

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