201677-59-0Relevant articles and documents
Modulation of catalyst reactivity for the chemoselective hydrogenation of a functionalized nitroarene: Preparation of a key intermediate in the synthesis of (R,R)-formoterol tartrate
Wilkinson, H. Scott,Hett, Robert,Tanoury, Gerald J.,Senanayake, Chris H.,Wald, Stephen A.
, p. 567 - 570 (2000)
In the synthesis of the β2-adrenoceptor agonist (R,R)-formterol, a key step in the synthesis was the development of a highly chemoselective reduction of (IR)-2-bromo-1-[3-nitro-4-(phenyl-methoxy)phenyl]ethan-1-ol to give (1R)-1-[3-amino-4-(phenyl-methoxy)phenyl]-2-bromoethan-1-ol. The aniline product was isolated as the corresponding formamide. The reaction required reduction of the nitro moiety in the presence of a phenyl benzyl ether, a secondary benzylic hydroxyl group, and a primary bromide, and with no racemization at the stereogenic carbinol carbon atom. The development of a synthetic methodology using heterogeneous catalytic hydrogenation to perform the required reduction was successful when a sulfur-based poison was added. The chemistry of sulfur-based poisons to temper the reacitivty of catalyst was studied in depth. The data show that the type of hydrogenation catalyst, the oxidation state of the poison, and the substituents on the sulfur atom had a dramatic effect on the chemoselectivity of the reaction. Dimethyl sulfide was the poison of choice, possessing all of the required characteristics for providing a highly chemoselective and high yielding reaction. The practicality and robustness of the process was demonstrated by preparing the final formamide product with high chemoselectivity, chemical yield, and product purity on a multi-kilogram scale.
CLASS OF BIFUNCTIONAL COMPOUNDS WITH QUATERNARY AMMONIUM SALT STRUCTURE
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Paragraph 0165, (2019/11/11)
The invention provides a class of compounds represented by formula (I), having bifunctional active quaternary ammonium salt structure of a β2-adrenoreceptor agonist and an M receptor antagonist, a pharmaceutically acceptable salt, solvate, and optical isomer thereof. A pharmaceutical composition comprising such a compound with quaternary ammonium salt structure, a method for preparing such a compound with quaternary ammonium salt structure and an intermediate thereof, and uses thereof in treating pulmonary disorders are also provided. The compounds of the invention have high selectivity to the M receptor subtype, and have less adverse reaction and lower toxic and side effects in the treatment of pulmonary diseases such as COPD and asthma.
PROCESS FOR THE PREPARATION OF ARFORMOTEROL OR SALT THEREOF
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Paragraph 0159, (2016/04/19)
Provided is an improved process for the preparation of arformoterol L-(+)-tartrate, and more specifically provided is a novel process for the preparation of arformoterol L-(+)-tartrate via arformoterol D-(?)-tartrate.
