Dr. James Wollack
Chemistry and Biochemistry
Three-step economical and green alternative to Donepezil intermediate
A three step economical and green alternative has been developed for the synthesis of the Donepezil intermediate. Donepezil is an acetylcholinesterase inhibitor used to improve cognitive functions in Alzheimer's disease (AD) patients. AD is a progressive neurodegenerative disorder characterized by the loss of memory and dementia and has been shown to cause the death of cholinergic neurons and a decline in acetylcholine. Multiple studies showed that the use of anticholinergic agents cause amnesia and learning disabilities which confirm the importance of acetylcholine against dementia. The use of acetylcholinesterase inhibitor inhibits the enzyme acetylcholinesterase increasing, thus, the levels of acetylcholine. The three steps synthesis proposed involve the conversion of 3,4-dimethoxycinnamic acid to 3-phenylpropionic acid via Pd/C catalysis followed by the conversion of 3-phenylpropionic acid to 5,6-dimethoxy-1-inandone via intramolecular Friedel-Craft acylation using ethyl acetate for extraction as a green alternative to dichloromethane. 5,6-dimethoxy-1-inandone and 4-Pyridinecarboxaldehyde were added together to form our Donepezil intermediate.