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

HRID 2408874Notes

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

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

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

Sources & evidence

ORD record: ord-60ba94cf0fb747fd9251aa25a6c34790
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815871B2

Reaction notes

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