468730-61-2

Upstream product

• 140-88-5 ethyl acrylate 
• 122948-57-6 ethyl 4-(((trifluoromethyl)sulfonyl)oxy)cyclohex-3-enecarboxylate 
• 190661-82-6 5-bromo-8-methoxy-2,3-dihydrobenzo[b][1,4]dioxine 
• 444108-41-2 3-(2,3-dihydro-8-methoxy-1,4-benzodioxin-5-yl)-1-buten-3-ol 
• 444108-40-1 8-methoxy-2,3-dihydrobenzo[b][1,4]dioxin-5-ylboronic acid 
• 444108-39-8 ethyl 4-(2,3-dihydro-8-methoxy-1,4-benzodioxin-5-yl)-3-cyclohexenecarboxylate 
• 7677-24-9 trimethylsilyl cyanide 

Relevant academic research and scientific papers

A practical synthesis of the PDE4 inhibitor, KW-4490

A practical and scalable synthesis of a PDE4 inhibitor KW-4490 (1) was developed. This improved synthesis features the construction of the 1-arylcyclohexene (9) by the Diels-Alder reaction followed by a newly established Brnsted acid-promoted hydrocyanation. Subsequent crystallization-induced dynamic resolution enabled the high-yield production of the desired cis-isomer (cis-8). The synthesis was achieved in seven steps in 37% overall yield.

Broonsted acid-promoted hydrocyanation of arylalkenes

Nonactivated arylalkenes are effectively converted to tertiary benzylic nitriles in the presence of triflic acid and trimethylsilyl cyanide. The hydrocyanation reactions result in good to excellent yield when electron-donating groups are substituted on the benzene ring. The reaction conditions are mild and relatively safe, notably without need for handling hazardous hydrogen cyanide gas, providing simple and easy access to tertiary benzylic nitriles. The reaction was applied to the preparation of a PDE4 inhibitor (3) as well as a series of analogues.