(S)-alpha,alpha-Diphenyl-3-pyrrolidineacetamide Chemical Properties

Boiling point:

419.1±35.0 °C(Predicted)

Density 

1.107±0.06 g/cm3(Predicted)

pka

9.46±0.10(Predicted)

CAS DataBase Reference

133099-11-3(CAS DataBase Reference)

(S)-alpha,alpha-Diphenyl-3-pyrrolidineacetamide Usage And Synthesis

Chemical Properties

lightbrown powder

Uses

(S)-2,2-Diphenyl-2-(pyrrolidin-3-yl)acetonitrile is a degradation product of darifenacin and also a darifenacin Cyano Pyrrolidine Impurity compound.

Synthesis

General procedure for the synthesis of (S)-2,2-diphenyl-2-(pyrrolidin-3-yl)acetonitrile from the compound (CAS: 851645-39-1): (S)-1-benzyl-3-(1-cyano-1,1-diphenylmethyl)pyrrolidine was dissolved in isopropyl acetate (in the ratio of about 1 g/10 mL), followed by addition of an equal volume of aqueous 1N hydrochloric acid solution. After performing liquid-liquid separation, the aqueous layer was extracted with an equal volume of isopropyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate and filtered. The solvent was evaporated under reduced pressure to give (S)-1-benzyl-3-(1-cyano-1,1-diphenylmethyl)pyrrolidine hydrochloride as a light yellow foamy solid (Note: this hydrochloride can also be prepared in the post-processing of Step B). To a stirred solution of (S)-1-benzyl-3-(1-cyano-1,1-diphenylmethyl)pyrrolidine hydrochloride (8.55 g, 21.98 mmol) in methanol (44 mL) was added palladium carbon (1.71 g) and ammonium formate (6.93 g, 109.9 mmol). The reaction mixture was heated to 50 °C with continuous stirring for 3 hours. After the reaction was complete, it was cooled to room temperature and water (20 mL) was added. The reaction mixture was filtered through a diatomaceous earth pad and washed with methanol (20 mL). The filtrate was collected and most of the methanol was removed under reduced pressure. The residue was mixed with isopropyl acetate (100 mL) and 10% aqueous sodium carbonate (50 mL). The organic and aqueous layers were separated and the aqueous layer was re-extracted with isopropyl acetate (50 mL). The organic layers were combined and dried with anhydrous sodium sulfate (20 g). The sodium sulfate was removed by filtration and washed with isopropyl acetate (20 mL). Finally, the solvent was removed under reduced pressure to give 5.75 g of the target intermediate as a light yellow oil (99.7% yield, 71% HPLC purity).

References

[1] Patent: WO2005/7645, 2005, A1. Location in patent: Page 59
[2] Patent: US2005/203167, 2005, A1. Location in patent: Page/Page column 17
[3] Patent: US2005/277688, 2005, A1. Location in patent: Page/Page column 11
[4] Patent: WO2004/41806, 2004, A2. Location in patent: Page 61
[5] Patent: WO2004/89892, 2004, A2. Location in patent: Page 80

(S)-alpha,alpha-Diphenyl-3-pyrrolidineacetamide(133099-11-3)Related Product Information

• Pyrrolidine
• N-Methyl-2-pyrrolidone
• Biphenyl
• Polyvinylpyrrolidone
• Acetamide
• Piracetam
• N-Vinyl-2-pyrrolidone
• METHYL-2-PYRROLIDONE
• (S)-alpha,alpha-Diphenyl-3-pyrrolidineacetamide L-tartaric acid salt
• Darifenacin
• 3-(S)-(1-Carbamoyl-1,1-diphenylmethyl)pyrrolidine
• (S)-alpha,alpha-Diphenyl-3-pyrrolidineacetamide