Iron Spurs C–H Bond Reactivity Organometallics: Catalyst creates drug scaffolds quickly

 

Iron catalyst transforms linear alkyl azides into cyclic amines via C–H functionalization.

read at 

http://cen.acs.org/articles/91/i18/Iron-Spurs-CH-Bond-Reactivity.html

http://cen.acs.org/articles/91/i18/Iron-Spurs-CH-Bond-Reactivity.html

http://cen.acs.org/articles/91/i18/Iron-Spurs-CH-Bond-Reactivity.html

Sweet Route to Steviamine

 

 

A concise synthesis of steviamine and three of its analogues is reported before testing for glycosidase inhibition

Read more at chemistry views

Replacing DEAD with recyclable reagents in the Mitsunobu reaction may lead to it being used for larger-scale industrial processes

Replacing a DEAD, Middle-aged Reagent

Replacing DEAD with recyclable reagents in the Mitsunobu reaction may lead to it being used for larger-scale industrial processes
Read more
at chemistryviews by David Bradley
http://www.chemistryviews.org/details/ezine/4634311/Replacing_a_DEAD_Middle-aged_Reagent.html

The Mitsunobu reaction is an organic reaction that converts an alcohol into a variety of functional groups, such as an ester, using triphenylphosphine and an azodicarboxylate such as diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) The alcohol undergoes an inversion of stereochemistry. It was discovered by Oyo Mitsunobu (1934–2003).

07 May 2013

An Improved and Efficient Process for the Production of Donepezil Hydrochloride: Substitution of Sodium Hydroxide for n-Butyl Lithium via Phase Transfer Catalysis

An Improved and Efficient Process for the Production of Donepezil Hydrochloride: Substitution of Sodium Hydroxide for n-Butyl Lithium via Phase Transfer Catalysis

Navanath Niphade, Anil Mali, Kunal Jagtap, Ramesh Chandra Ojha, Pravinchandra J. Vankawala and Vijayavitthal T. Mathad

 Department of Process Research and Development, Megafine Pharma (P) Ltd., 201, Lakhmapur, Dindori, Nashik 422 - 202, Maharashtra, India

 

Org. Process Res. Dev., 2008, 12 (4), pp 731–735

 

Publication Date (Web): May 30, 2008 (Article)

DOI: 10.1021/op800066m

 http://pubs.acs.org/doi/abs/10.1021/op800066m?prevSearch=donepezil&searchHistoryKey=

 

 A simple, efficient and highly economic process for the production of donepezil hydrochloride (1), an anti-Alzheimer drug is reported. The process relies upon improved and large-scale synthesis of a key intermediate: 1-benzylpiperidine-4-carboxaldehyde (2), and the introduction of operationally simple chemistry at the penultimate stage wherein 2 is reacted with 5,6-dimethoxy indanone (3) in the presence of sodium hydroxide and a phase transfer catalyst (PTC) in a biphasic solvent to furnish the intermediate 4, which is reduced and directly treated with hydrochloric acid to furnish highly pure donepezil hydrochloride with desired polymorphic form. The improved process provides donepezil hydrochloride at considerably lower cost and allows the omission of hazardous chemicals.

 

 

Synthesis of Donepezil Hydrochloride via Chemoselective Hydrogenation

Synthesis of Donepezil Hydrochloride via Chemoselective Hydrogenation

 Org. Process Res. Development

 http://pubs.acs.org/doi/abs/10.1021/op400007p

 

Ajay Singh Rawat, Sachin Pande, Nilay Bhatt, Raju Kharatkar, Chandrakant Belwal, and Anand Vardhan

 

Sterling Biotech Limited, Jambusar State Highway, Village Masar 391421, Taluka, Padra, Distt: Vadodara Gujarat India

 

Articles ASAP (As Soon As Publishable)

Publication Date (Web): April 9, 2013 (Article)

DOI: 10.1021/op400007p

 

 A simple and highly chemoselective and cost-effective process for the synthesis of Donepezil 1 has been developed for commercial production. In the process, the exocyclic double bond is mainly targeted for catalytic hydrogenation in the presence of an N-benzyl group using sulfur, nitrogen, and phosphorous catalyst modifiers. In some cases, catalytic hydrogenation with Pd on charcoal also produced an undesired side product along with the main product due to over reduction. Removal of these impurities by crystallization, column chromatography, or other means of purification makes the process tedious and lengthy, and sometimes it is difficult to achieve the impurity limit as per International Conference on Harmonisation (ICH) guidelines for active pharmaceutical ingredients. In the present investigation we report the synthesis of Donepezil 1 in pure form wherein the debenzyl impurity is within the acceptable limits.

Aesica, University of Nottingham to develop novel drug synthesis method

Aesica, University of Nottingham to develop novel drug synthesis method
Aesica, a global contract manufacturing organisation (CMO), has announced a partnership with the UK's University of Nottingham to explore the development of alternative methods in amide bond synthesis
read at
http://www.pharmaceutical-technology.com/news/newsaesica-university-of-nottingham-to-develop-novel-drug-synthesis-method

Copper-Mediated Cyanation of Aryl Halides by Activation of Benzyl Cyanide as the Cyanide Source

Cyanation Reactions

Copper-Mediated Cyanation of Aryl Halides by Activation of Benzyl Cyanide as the Cyanide SourceQiaodong Wen, Jisong Jin, Yuncai Mei, Ping Lu and Yanguang Wang Article first published online: 6 MAY 2013 | DOI: 10.1002/ejoc.201300052 European Journal of Organic Chemistry   An efficient, copper-mediated cascade synthesis of aryl nitriles from aryl halides using benzyl cyanide as the cyanide source is described. Compared with traditional copper-mediated cyanation reactions, this approach effectively avoided the use of toxic MCN and low soluble reagents. Furthermore, C–H oxidation and C–CN cleavage are proposed to be involved in this cascade process. Aryl nitriles were efficiently synthesized through copper-mediated cyanation of aryl halides using benzyl cyanide as the cyanide source. Aryl halides with various substituents on the aromatic ring afforded the corresponding aryl nitriles in 32–97 % yields (25 examples). This reaction could also be carried on a gram scale by using commercially available reagents. Additionally, a C–H bond oxidation and a C–CN cleavage are proposed to be involved in this cascade process.