(S)-1-Benzyl 2-Methyl 4-Oxopyrrolidine-1,2-Dicarboxylate

(S)-1-Benzyl 2-Methyl 4-Oxopyrrolidine-1,2-Dicarboxylate Property

Boiling point:

422.1±45.0 °C(Predicted)

Density 

1.306±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

Chloroform, Dichloromethane, Dimethylsulfoxide, Ethyl Acetate

form 

Oil

pka

-3.91±0.40(Predicted)

color 

Light Yellow

Safety

HazardClass 

IRRITANT

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P321Specific treatment (see … on this label).

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

(S)-1-Benzyl 2-Methyl 4-Oxopyrrolidine-1,2-Dicarboxylate Chemical Properties,Usage,Production

Chemical Properties

Light Yellow Oil

Uses

(S)-1-Benzyl 2-Methyl 4-Oxopyrrolidine-1,2-Dicarboxylate is used in the preparation of dipeptidyl peptidase IV inhibitors and (hydroxy)(carbamoyl)pyrimidinones as potent and orally bioavailable HIV integrase inhibitors.

Synthesis

General procedure for the synthesis of N-Cbz-4-oxo-L-proline methyl ester from (2S,4S)-N-CBZ-4-hydroxyproline methyl ester: Dess-Martin periodinane (3.0 g, 7.1 mmol) was added batchwise to a solution of compound (2S,4S)-N-CBZ-4-hydroxyproline methyl ester (1.0 g , 3.6 mmol) in a solution of dichloromethane (DCM, 20 mL). After addition, the reaction mixture was stirred at room temperature for 1.0 hour. After completion of the reaction, the mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate, v/v=5/1) to afford N-Cbz-4-oxo-L-proline methyl ester as a yellow oil (0.79 g, 79.5% yield). The structure of the compound was confirmed by the following spectral data: 1H NMR (400 MHz, CDCl3) δ (ppm): 7.47 (d, 2H, J=8.24 Hz), 7.38 (d, 2H, J=8.24 Hz), 7.24 (m, 1H), 5.09 (s, 2H), 4.18 (t, 1H), 3.68 (s, 3H). 3.38 (m, 1H), 3.32 (m, 1H), 2.21 (m, 1H), 1.96 (m, 1H).

References

[1] Patent: WO2014/82380, 2014, A1. Location in patent: Paragraph 00510; 00513
[2] Patent: EP2730572, 2014, A1. Location in patent: Paragraph 0706-0716
[3] Patent: EP2730572, 2015, B1. Location in patent: Paragraph 0706-0716
[4] Patent: WO2014/131315, 2014, A1. Location in patent: Page/Page column 176
[5] Patent: EP2730572, 2015, B1. Location in patent: Paragraph 0700; 0708