Benzyl 4-hydroxy-1-piperidinecarboxylate

Benzyl 4-hydroxy-1-piperidinecarboxylate Property

Boiling point:

167 °C/0.2 mmHg (lit.)

Density 

1.554 g/mL at 25 °C (lit.)

refractive index 

n20/D 1.543(lit.)

Flash point:

>230 °F

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

form 

Oil

pka

14.79±0.20(Predicted)

color 

Orange

InChI

InChI=1S/C13H17NO3/c15-12-6-8-14(9-7-12)13(16)17-10-11-4-2-1-3-5-11/h1-5,12,15H,6-10H2

InChIKey

JKIUUDJOCYHIGY-UHFFFAOYSA-N

SMILES

N1(C(OCC2=CC=CC=C2)=O)CCC(O)CC1

CAS DataBase Reference

95798-23-5(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36-37/39

WGK Germany 

3

Hazard Note 

Irritant

HS Code 

2933399990

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.

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

Benzyl 4-hydroxy-1-piperidinecarboxylate Chemical Properties,Usage,Production

Uses

Reactant for synthesis of:
Orally bioavailable P2Y12 antagonists for inhibition of platelet aggregation
Piperidine derivatives
Molecular rods
Oxazolidinone-quinolone hybrids and their antibacterial activity
Cyclic prodrug of RGD peptidomimetic

Reactant for oxidation of alcohols

Synthesis

General procedure for the synthesis of N-Benzyloxycarbonyl-4-hydroxypiperidine from 4-hydroxypiperidine and benzyl chloroformate: over 30 min, benzyl chloroformate (8.55 mL; 60 mmol) was slowly added dropwise to a well-stirred 4-hydroxypiperidine (5 g; 49.44 mmol), a 1N aqueous NaOH solution (60 mL; 60 mmol) and dioxane (60 mL) in a in a cooled mixture. After dropwise addition, the reaction mixture was continued to stir for 30 minutes. Upon completion of the reaction, the reaction mixture was treated with water and subsequently concentrated and acidified with hydrochloric acid to pH 2. The acidified aqueous phase was extracted with EtOAc, the organic phases were combined, washed with water and saturated brine in that order, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by fast column chromatography (silica gel was the stationary phase, and the eluents were petroleum ether with 50% dichloromethane (60-80 °C) and 10% acetonitrile containing 2% methanol in chloroform solution). The final product was 12.5 g (99% yield) of N-Cbz-4-hydroxypiperidine as an oil; mass spectrum (chemical ionization): m/z 236 (M++1), 218, 192, 174, 91.

References

[1] Patent: WO2005/35495, 2005, A2. Location in patent: Page/Page column 129
[2] Patent: US7759387, 2010, B2. Location in patent: Page/Page column 113
[3] Bioorganic Chemistry, 2002, vol. 30, # 4, p. 285 - 301
[4] Chemistry - A European Journal, 2007, vol. 13, # 17, p. 4859 - 4872
[5] Angewandte Chemie - International Edition, 2014, vol. 53, # 12, p. 3236 - 3240