Water → HCID 59614365、化合物

HRID 409465ノート

反応式

HRID 409465 の反応式
[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]

参加物

7

反応物 4

HCID 962WaterHCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydride2 回HCID 59614349HCID 59614349、化合物

生成物 1

HCID 59614365HCID 59614365、化合物収率 128%

試薬・触媒・溶媒 2

HCID 11026Titanium isopropoxide触媒HCID 887Methanol溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-e8ac3059f9334ae3a531bbe11fa66b4d
出典データセット
uspto-grants-2014_06
特許番号
US08759365B2

反応ノート

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