4-Aminobenzonitrile → HCID 66653188, compound

HRID 1524271Notes

Reaction equation

[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[C:17]([N:21]2[CH2:25][CH2:24][CH2:23][C@@H:22]2[C:26](O)=[O:27])[CH:18]=[CH:19][CH:20]=1)=[O:14])[CH3:11].P(Cl)(Cl)(Cl)=O.O(Cl)Cl>N1C=CC=CC=1.O>[CH2:10]([O:12][C:13](=[O:14])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]2[CH2:25][CH2:24][CH2:23][C@@H:22]2[C:26](=[O:27])[NH:1][C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=2)[CH:16]=1)[CH3:11]

Participants

Conditions

Temperature: 0 °C

Procedure

Cool a solution of 4-aminobenzonitrile (0.05 g, 0.42 mmol) in pyridine (2 mL) to 0° C., and add (R)-1-(3-ethoxycarbonyl-phenyl)-pyrrolidine-2-carboxylic acid (0.10 g, 0.38 mmol), followed by phosphorous oxychloride (0.04 mL, 0.43 mmol). Stir the mixture at 0° C. for 2 h followed by addition of a second portion of phosphrous oxychloride (0.04 mL, 0.43 mmol). Stir the mixture at 0° C. for an additional 1 hour. Dilute the mixture with water and extract with EtOAc. Wash the combined organic phase with a saturated aqueous solution of sodium bicarbonate followed by a saturated aqueous solution of ammonium chloride and then brine. Dry the mixture over anhydrous sodium sulfate and concentrated under reduced pressure to provide 0.052 g of 3-[(R)-2-(4-cyano-phenylcarbamoyl)-pyrrolidin-1-yl]-benzoic acid ethyl ester as a solid.

Workup

stirringStir the mixture at 0° C. for an additional 1 hour
extractionextract with EtOAc
washWash the combined organic phase with a saturated aqueous solution of sodium bicarbonate
dry with materialDry the mixture over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-3cec5c42070242ae863911ea900ff9c6
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09079880B2

Reaction notes

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