(S)-1-(2-Chloroacetyl)pyrrolidine-2-carboxaMide Chemical Properties

Melting point:

133-137℃ (isopropyl ether )

Boiling point:

442.5±45.0 °C(Predicted)

Density 

1.353±0.06 g/cm3(Predicted)

storage temp. 

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

solubility 

Chloroform (Slightly, Sonicated), DMSO (Slightly), Methanol (Very Slightly)

form 

Solid

pka

15.56±0.20(Predicted)

color 

White to Pale Beige

InChI

InChI=1S/C7H11ClN2O2/c8-4-6(11)10-3-1-2-5(10)7(9)12/h5H,1-4H2,(H2,9,12)/t5-/m0/s1

InChIKey

YKDRUBGIBPCRBH-YFKPBYRVSA-N

SMILES

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

Safety Information

HS Code 

2924190090

(S)-1-(2-Chloroacetyl)pyrrolidine-2-carboxaMide Usage And Synthesis

Uses

(S)-1-(2-Chloroacetyl)pyrrolidine-2-carboxamide is used in the synthesis of Vildagliptin (V305000), an oral anti-diabetic drug, and its impurities (H971380) (Impurity A).

Synthesis

L-prolinamide (11.2 g, 100 mmol) was added to a tetrahydrofuran solution (200 mL) of chloroacetyl chloride (11.5 g, 100 mmol) that had been pre-cooled to 0°C. The reaction system was kept at 0°C. After 30 min, potassium carbonate (27.3 g, 200 mmol) was added to the reaction mixture, and stirring was continued for 1 hour at 0°C. Subsequently, the reaction mixture was warmed up to room temperature and stirring was continued for 3 hr. The progress of the reaction was monitored by LC until L-prolinamide was completely consumed. After completion of the reaction, the reaction mixture was filtered and the filter cake was washed with tetrahydrofuran (50 mL) and the filtrates were combined. The solvent was removed by rotary evaporation and the oily residue obtained was dissolved in ethyl acetate. The resulting ethyl acetate solution was washed with water (50 mL x 2) and dried over anhydrous sodium sulfate for 2 hours. After filtration to remove the desiccant, the filtrate was concentrated to give 17.2 g (S)-1-(2-chloroacetyl)pyrrolidine-2-carboxamide (colorless oily) in 90.7% yield.

References

[1] Patent: CN103896819, 2016, B. Location in patent: Paragraph 0017; 0018; 0019
[2] Patent: CN105503878, 2016, A. Location in patent: Paragraph 0017
[3] Patent: CN105884669, 2016, A. Location in patent: Paragraph 0059-0063
[4] Journal of Medicinal Chemistry, 2003, vol. 46, # 13, p. 2774 - 2789
[5] Journal of Medicinal Chemistry, 2002, vol. 45, # 12, p. 2362 - 2365

(S)-1-(2-Chloroacetyl)pyrrolidine-2-carboxaMide(214398-99-9)Related Product Information

• 1-(CHLOROACETYL)-L-PROLINE METHYL ESTER
• vildagliptin Impurity L
• vildagliptin Impurity R
• (2S)-1-(Chloroacetyl)-2-pyrrolidinecarbonitrile
• (S)-Pyrrolidine-2-carbonitrile hydrochloride
• vildagliptin Impurity Q
• Vildagliptin Related Compound F
• Vildagliptin Related Compound H
• vildagliptin Impurity O
• Vildagliptin Related Compound E
• CHLOROAC-PRO-OH
• 5-Vinylpyrrolidone
• Vildagliptin Related Compound G
• VILDAGLIPTIN
• N-acetic acid-1-aMino-3-adaMantanol
• Vildagliptin IMpurity 2 (Mixture of DiastereoMers)
• Dichloroacetyl chloride
• CYCLO(-GLY-PRO)