3-Aminobenzonitrile → trans-3-(3-Bromo-phenyl)-4-(3-cyano-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1524288Notes

Reaction equation

HRID 1524288 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=2)[C@H:10]([C:20](O)=[O:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[C:27]#[N:28].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1.O>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([C:20](=[O:21])[NH:23][C:24]2[CH:31]=[CH:30][CH:29]=[C:26]([C:27]#[N:28])[CH:25]=2)[C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=2)[CH2:12]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 167023-AminobenzonitrileHCID 24813Phosphorus oxychlorideHCID 2762118Trans-4-(3-bromophenyl)-1-Boc-pyrrolidine-3-carboxylic acid

Product 1

HCID 68089325trans-3-(3-Bromo-phenyl)-4-(3-cyano-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 83.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

Cool a solution of trans-4-(3-bromo-phenyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (0.50 g, 1.35 mmol) in pyridine (5 mL), to 0° C., and add 3-aminobenzonitrile (0.18 g, 1.48 mmol) followed by phosphorous oxychloride (0.14 mL, 1.50 mmol). Stir the mixture at 0° C. for 1 h then dilute with water. Extract the mixture with EtOAc and wash the combined organic portion with a 2 N solution of hydrochloric acid until the pH of the aqueous washings is strongly acidic. Wash the organic phase with brine then dry over anhydrous sodium sulfate and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography to provide 0.53 g of trans-3-(3-bromo-phenyl)-4-(3-cyano-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a solid.

Workup

  1. extractionExtract the mixture with EtOAc
  2. washwash the combined organic portion with a 2 N solution of hydrochloric acid until the pH of the aqueous washings
  3. washWash the organic phase with brine
  4. dry with materialthen dry over anhydrous sodium sulfate
  5. concentrationconcentrate under reduced pressure
  6. customPurify the residue by flash silica gel chromatography

Sources & evidence

ORD record
ord-8588fe25c8d84a39abb4408f90e4ab2e
Source dataset
uspto-grants-2015_07
Patent number
US09079880B2

Reaction notes

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