FMOC-D-PIPECOLIC ACID

FMOC-D-PIPECOLIC ACID Property

Melting point:

149-153°C

Boiling point:

561.6±43.0 °C(Predicted)

Density 

1.293±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

soluble in Methanol

pka

3.97±0.20(Predicted)

form 

Solid

color 

White to pale brown

optical activity

20.768°(C=0.01g/ml DMF)

BRN 

5485101

CAS DataBase Reference

101555-63-9(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36-37/39

RIDADR 

3077

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

29333990

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.

FMOC-D-PIPECOLIC ACID Chemical Properties,Usage,Production

Chemical Properties

white to light yellow crystal powde

Uses

(R)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic Acid is a building block used as a reactant in the preparation cyclic tetrapeptide derivatives as histone deacetylase inhibitors and antitumor agents.

reaction suitability

reaction type: Fmoc solid-phase peptide synthesis

Synthesis

The general procedure for the synthesis of (R)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid from the compound (CAS: 102774-86-7) and L-2-piperidinic acid is as follows: 1. L-piperidine acid (3.6 g, 38.7 mmol) was dissolved in 40 mL of 10% sodium carbonate solution in a round-bottomed flask and stirred at room temperature for 5 min. 2. Fmoc-OSu (8.5 g, 34.8 mmol) dissolved in 35 mL of dioxane was added to the above solution and the reaction mixture was stirred overnight. 3. Upon completion of the reaction, water was added and the aqueous layer was extracted with ethyl acetate. 4. The aqueous layer was acidified to pH=2 by adding concentrated hydrochloric acid. 5. The acidified aqueous layer was extracted with ethyl acetate (3 x 40 mL). 6. 6. The organic phases were combined and washed sequentially with 1N HCl and brine, then dried with anhydrous magnesium sulfate and concentrated in vacuum to obtain a colorless oily liquid. 7. The oily liquid was dissolved in ether and cooled to give a fluffy white solid, which was washed with hexane and dried to give (S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (8.2 g, 38.7 mmol, 83% yield). Product characterization data: - TLC (hexane:EtOAc:TFA = 1:1:0.2): rf = 0.60 - HPLC (gradient A) retention time = 24.6-24.8 min - 1H NMR (300 MHz, CDCl3) δ = 1.28-1.53 (m, 2H), 1.69-1.82 (m, 3H), 2.19-2.37 (m, 1H), 3.15 (t, 1H, J = 13.2 Hz), 4.05-4.33 (m, 2H), 4.37-4.49 (m, 2H), 4.76- 5.05 (m, 1H), 7.28-7.41 (m, 4H), 7.55-7.62 (m, 2H), 1.77 (s, 2H). - 13C NMR (75 MHz, CDCl3) δ = 20.72, 24.70, 26.55, 41.94, 47.25, 54.19, 67.86, 119.97, 125.08, 127.07, 127.68, 141.33, 143.89, 156.65, 177.36. - MS (ESI) m/z: 352.66 [M + H]+, calculated: 352.40 [M + H]+.

References

[1] Patent: WO2013/91900, 2013, A1. Location in patent: Page/Page column 41