4-ChloroMethyl-1-cyclopentyl-2-trifluoroMethyl-benzene Property

Boiling point:

293.7±35.0 °C(Predicted)

Density 

1.226±0.06 g/cm3(Predicted)

InChI

InChI=1S/C13H14ClF3/c14-8-9-5-6-11(10-3-1-2-4-10)12(7-9)13(15,16)17/h5-7,10H,1-4,8H2

InChIKey

NUFXNFBJDGCADP-UHFFFAOYSA-N

SMILES

C1(C2CCCC2)=CC=C(CCl)C=C1C(F)(F)F

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

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

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

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.

4-ChloroMethyl-1-cyclopentyl-2-trifluoroMethyl-benzene Chemical Properties,Usage,Production

Uses

4-chloromethyl-1-cyclopentyl-2-(trifluoromethyl)benzene is a precursor of APD334, which is a potent functional antagonist of S1P1 and has a favourable PK/PD profile, producing robust lymphocyte lowering at relatively low plasma concentrations in several preclinical species[1].

Synthesis

A two-step scalable process was developed starting from commercially available and inexpensive starting materials. An iron(III) chloride-catalyzed aryl–alkyl cross-coupling reaction provided the intermediate 1-cyclopentyl-2-(trifluoromethyl)benzene (9), which was converted to the target building block 4-chloromethyl-1-cyclopentyl-2-(trifluoromethyl)benzene by a direct regioselective chloromethylation reaction with trioxane/thionyl chloride or chlorosulfonic acid in sulfuric acid[2].

References

[1] Daniel J. Buzard*. “Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor.” ACS Medicinal Chemistry Letters 5 12 (2014): 1313–1317.
[2] Dipanjan Sengupta. “An Efficient Scale-Up Process for the Preparation of the APD334 Precursor 4-Chloromethyl-1-cyclopentyl-2-(trifluoromethyl)benzene.” Organic Process Research Development 19 6 (2015): 618–623.