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

HRID 403412

반응식

HRID 403412 반응식
[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]

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 8857Ethyl Acetate용매2회

반응 조건

온도
5 °C

실험 절차

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%.

후처리

  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

출처 및 근거

ORD 기록
ord-bfe975cdba4a463484dcb7b4abb4c63a
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748374B2

연결된 노트

불러오는 중…