Dimethylamine → 3(S)-[(3-chloro-4-fluorophenyl)-(3-dimethylamino propyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 660117Notes

Reaction equation

HRID 660117 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([N:13]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[C:20]([Cl:25])[CH:19]=2)[CH2:14][CH2:15][CH2:16]Cl)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:26][NH:27][CH3:28].[I-].[Na+].O>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([N:13]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[C:20]([Cl:25])[CH:19]=2)[CH2:14][CH2:15][CH2:16][N:27]([CH3:28])[CH3:26])[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 674DimethylamineHCID 962WaterHCID 5238Sodium IodideHCID 666572323(S)-[(3-chloro-4-fluorophenyl)-(3-chloropropyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666572703(S)-[(3-chloro-4-fluorophenyl)-(3-dimethylamino propyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

3(S)-[(3-chloro-4-fluorophenyl)-(3-chloropropyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester (0.5 g, 1.24 mmol), 50% dimethylamine solution (1 ml) and sodium iodide (0.37 g, 2.5 mmol) were suspended in DMF (3 ml), followed by stirring at 60° C. for 4 hours. After cooling to room temperature, water was added to the reaction solution, and extraction with ethyl acetate was conducted. The organic layer was dried over sodium sulfate, and the solvent was then distilled off under reduced pressure. The residue was purified with basic silica gel column chromatography (ethyl acetate), and the purified product was then concentrated under reduced pressure to thereby obtain 0.36 g of oily colorless 3(S)-[(3-chloro-4-fluorophenyl)-(3-dimethylamino propyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. temperatureAfter cooling to room temperature
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. distillationthe solvent was then distilled off under reduced pressure
  4. customThe residue was purified with basic silica gel column chromatography (ethyl acetate)
  5. concentrationthe purified product was then concentrated under reduced pressure

Sources & evidence

ORD record
ord-565cfca6e21e4fd6b05eac509334b8b7
Source dataset
uspto-grants-2011_12
Patent number
US08084442B2

Reaction notes

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