Water → HCID 59614365, compound

HRID 409465Notes

Reaction equation

HRID 409465 reaction equation
[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]

Participants

7

Reactant 4

HCID 962WaterHCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydride2×HCID 59614349HCID 59614349, compound

Product 1

HCID 59614365HCID 59614365, compoundYield 128%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-e8ac3059f9334ae3a531bbe11fa66b4d
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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