ethyl 1-benzyl-5,5-difluoro-4-oxopiperidine-3-carboxylate

ethyl 1-benzyl-5,5-difluoro-4-oxopiperidine-3-carboxylate Property

Boiling point:

365.6±42.0 °C(Predicted)

Density 

1.25±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

pka

6.93±0.40(Predicted)

Appearance

off-white to yellow solid

Safety

HS Code 

2933399990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H314Causes severe skin burns and eye damage

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

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

P301+P330+P331IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

P363Wash contaminated clothing before reuse.

P405Store locked up.

P501Dispose of contents/container to..…

ethyl 1-benzyl-5,5-difluoro-4-oxopiperidine-3-carboxylate Chemical Properties,Usage,Production

Synthesis

The reaction system was cooled to -78 °C under nitrogen protection and n-butyllithium (BuLi, 1.6 M hexane solution, 8.52 mL, 13.64 mmol) was slowly added to a tetrahydrofuran (THF, 150 mL) solution of diisopropylamine (2.08 mL, 14.9 mmol). after 45 min, N-(3-ethoxy-2,2-difluoro-3-oxo propyl)-N-benzyl-β-alanine ethyl ester (compound W, 2.13 g, 6.2 mmol) to a solution of THF (50 mL). The cooling bath was removed and the reaction mixture was allowed to warm slowly to room temperature and stirred overnight. Upon completion of the reaction, the reaction was quenched by the addition of an aqueous solution of ammonium chloride (NH4Cl, 200 mL) and the organic and aqueous layers were separated. The aqueous phase was extracted with ethyl acetate (EtOAc, 3 x 150 mL). All organic layers were combined, washed with saturated brine and dried over anhydrous sodium sulfate (Na2SO4). After concentration under reduced pressure, the residue was purified by fast column chromatography (FC, eluent: EtOAc/heptane=1:9) to afford ethyl 1-benzyl-5,5-difluoro-4-oxo-piperidine-3-carboxylate (1.5 g, 81% yield).LC-MS analysis: retention time (Rut)=1.04 min, mass spectra (ES+) m/z =298.22.

References

[1] Patent: WO2005/40120, 2005, A1. Location in patent: Page/Page column 18; 31
[2] Patent: US2015/274652, 2015, A1. Location in patent: Paragraph 0237; 0242; 0243
[3] Patent: WO2016/126869, 2016, A1. Location in patent: Paragraph 0155