Water → HCID 59614365, 화합물

HRID 409465노트

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HRID 409465 반응식
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][CH3:14])[CH2:11][C:10](=O)[C@@H:9]1[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:23][C:24]([F:38])([F:37])[C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:28][NH2:29].[BH4-].[Na+].O>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][CH3:14])[CH2:11][C@H:10]([NH:29][CH2:28][C:27]2[CH:30]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:32]=[C:25]([C:24]([F:23])([F:37])[F:38])[CH:26]=2)[C@@H:9]1[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 962WaterHCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydride2회HCID 59614349HCID 59614349, 화합물

생성물 1

HCID 59614365HCID 59614365, 화합물수율 128%

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매HCID 887Methanol용매

실험 절차

To a solution (2S,5R)-2-benzyl-5-ethyl-3-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (0.038 mmol; 25.1 mg) and 3,5-bis(trifluoromethyl)benzylamine (0.166 mmol; 40.4 mg) in MeOH (0.4 mL) is added titanium(IV) isopropoxide (0.1 mmol; 28.4 mg). After stirring for 6 hours, NaBH4 (0.125 mmol; 4.8 mg) is added to the reaction mixture at 0° C. After stirring for 1.5 hours at room temperature, another NaBH4 (0.041 mmol; 1.6 mg) is added to the mixture at the same temperature. After stirring for additional 45 minutes, H2O is added to the mixture. The mixture is filtered and concentrated under reduced pressure. Water and dichloromethane are added to the residue. The organic layer after dried is separated, concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc) to give (2S,3S,5R)-2-benzyl-3-(3,5-bis-trifluoromethyl-benzylamino)-5-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (25.8 mg, 59%); ESI-MS m/z: 531 [M+1]+, Retention time 4.55 min (condition B).

후처리

  1. stirringAfter stirring for 1.5 hours at room temperature
  2. stirringAfter stirring for additional 45 minutes
  3. filtrationThe mixture is filtered
  4. concentrationconcentrated under reduced pressure
  5. additionWater and dichloromethane are added to the residue
  6. customThe organic layer after dried
  7. customis separated
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc)

출처 및 근거

ORD 기록
ord-e8ac3059f9334ae3a531bbe11fa66b4d
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759365B2

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