(2S)-1-(Chloroacetyl)-2-pyrrolidinecarbonitrile Chemical Properties

Melting point:

52-53 °C

Boiling point:

363.1±37.0 °C(Predicted)

Density 

1.27±0.1 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

-4.65±0.40(Predicted)

color 

Pale Yellow to Light Brown

optical activity

Consistent with structure

Stability:

Hygroscopic

InChI

InChI=1S/C7H9ClN2O/c8-4-7(11)10-3-1-2-6(10)5-9/h6H,1-4H2/t6-/m0/s1

InChIKey

YCWRPKBYQZOLCD-LURJTMIESA-N

SMILES

N1(C(CCl)=O)CCC[C@H]1C#N

Safety Information

HS Code 

2933998090

(2S)-1-(Chloroacetyl)-2-pyrrolidinecarbonitrile Usage And Synthesis

Chemical Properties

White crystals

Uses

(2S)-1-(2-Chloroacetyl)-2-9-pyrrolidinecarbonitrile is a key intermediate for dipeptidyl peptidase IV inhibitor Vildagliptin (V305000).

Synthesis

A method for the preparation of (S)-1-(2-chloroacetyl)-2-cyanopyrrolidine comprising the steps of dissolving L-prolinamide (0.175 mol) and potassium carbonate (0.348 mol) in 400 mL of acetonitrile, and slowly adding 16 mL (0.2 mol) of chloroacetyl chloride dropwise (dropwise time of 2-3 hrs.) at 0-15°C. After the dropwise addition, the reaction mixture was stirred overnight at room temperature and the reaction was monitored by TLC until complete. Upon completion of the reaction, the mixture was stirred at 0-15°C and 13.4 mL to 0.094 mol of 44 was slowly added, followed by stirring at 25°C overnight and again the reaction was confirmed complete by TLC. Subsequently, the reaction solution was rotary evaporated to dryness and 20 mL of ethyl acetate was added to the residue. An excess of trifluoroacetic anhydride (TFAA) was added to the reaction vessel, and the residue was dissolved in 150 mL of ethyl acetate and the pH was adjusted with sodium carbonate solution to 8. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting oil was left overnight to cure (if not cured, crystalline species could be added), resulting in a light brown solid (target compound) in 92% yield.

References

[1] Patent: CN106045891, 2016, A. Location in patent: Paragraph 0046; 0047-0049
[2] Patent: CN105523985, 2016, A. Location in patent: Paragraph 0054; 0055
[3] Patent: CN107501154, 2017, A. Location in patent: Paragraph 0068-0108
[4] Patent: US2008/167479, 2008, A1. Location in patent: Page/Page column 5
[5] Patent: US6432969, 2002, B1

(2S)-1-(Chloroacetyl)-2-pyrrolidinecarbonitrile(207557-35-5)Related Product Information

• 1-Methylpyrrolidine
• Pyrrolidine
• Acetylacetone
• Chloroacetyl chloride
• Acetylferrocene
• (S)-Pyrrolidine-2-carbonitrile hydrochloride
• N-ACETYL-L-TYROSINE ETHYL ESTER
• 2-Acetyl pyrrole
• Vildagliptin
• (S)-1-N-CBZ-2-CYANO-PYRROLIDINE
• Vildagliptin Related Compound A
• vildagliptin Impurity E
• (S)-PYRROLIDINE-2-CARBONITRILE
• Vildagliptin Impurity 10
• vildagliptin Impurity R
• vildagliptin Impurity Q
• Vildagliptin Impurity 6
• Vildagliptin IMpurity 2 (Mixture of DiastereoMers)