3-CYCLOPENTYLACRYLONITRILE Chemical Properties

Boiling point:

209.0±9.0 °C(Predicted)

Density 

1.027±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

form 

solid

Appearance

Colorless to light yellow Liquid

InChI

InChI=1S/C8H11N/c9-7-3-6-8-4-1-2-5-8/h3,6,8H,1-2,4-5H2

InChIKey

VMELXYJYSXXORF-UHFFFAOYSA-N

SMILES

C(#N)C=CC1CCCC1

Safety Information

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

2926907090

Storage Class

11 - Combustible Solids

3-CYCLOPENTYLACRYLONITRILE Usage And Synthesis

Uses

3-Cyclopentylacrylonitrile and its derivatives are used in the preparation of ruxolitinib intermediates and trasitinib phosphate. It is associated with diseases such as thrombocytosis, true erythrocytosis and primary myelofibrosis.

Synthesis

Step 1. A solution of diethyl cyanomethylphosphate (39.9 mL, 0.246 mol) in THF (300 mL) was added slowly and dropwise to a solution of 1.0 M potassium tert-butoxide in THF (235 mL) at 0 °C. The ice bath was removed and the reaction mixture was gradually warmed to room temperature and subsequently cooled to 0 °C again. At this temperature, a solution of cyclopentyl formaldehyde (22.0 g, 0.224 mol) in THF (60 mL) was added slowly and dropwise. The ice bath was removed and the reaction mixture was warmed to ambient temperature and stirred continuously for 64 hours. Upon completion of the reaction, the mixture was partitioned between ether and water, and the aqueous phase was extracted three times with ether followed by two extractions with ethyl acetate. The organic phases were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 24.4 g (89% yield) of a mixture of (2E)- and (2Z)-3-cyclopentylacrylonitrile, which was used in the subsequent steps without further purification.1H NMR (400 MHz, CDCl3): δ 6.69 (dd, 1H, trans olefin), 6.37 (t, 1H, cis-olefin), 5.29 (dd, 1H, trans-olefin), 5.20 (d, 1H, cis-olefin), 3.07-2.95 (m, 1H, cis-product), 2.64-2.52 (m, 1H, trans-product), 1.98-1.26 (m, 16H).

References

[1] Journal of Catalysis, 2003, vol. 218, # 1, p. 191 - 200
[2] Patent: EP2349260, 2016, B1. Location in patent: Paragraph 0111
[3] Patent: CN105418616, 2016, A. Location in patent: Paragraph 0110; 0111
[4] Patent: WO2011/31554, 2011, A2. Location in patent: Page/Page column 147-148