852237-40-2Relevant articles and documents
Practical synthesis of chiral 2-morpholine: (4-Benzylmorpholin-2-(s)-yl)- (tetrahydropyran-4-yl) Methanone mesylate, a useful pharmaceutical intermediate
Kopach, Michael E.,Singh, Utpal K.,Kobierski, Michael E.,Trankle, William G.,Murray, Michael M.,Pietz, Mark A.,Forst, Mindy B.,Stephenson, Gregory A.,Mancuso, Vincent,Giard, Thierry,Vanmarsenille, Michel,De France, Thierry
experimental part, p. 209 - 224 (2010/04/22)
A commercial synthesis was developed for the production of (4-benzylmorpholin-2-(S)-yl)-(tetrahydropyran-4-yl) methanone mesylate, la, a key starting material for a phase 2, new investigational drug candidate at Eli Lilly and Company. The target compound was produced in the clinical pilot plant by the combination of two key steps: resolution of a morpholine amide intermediate to install the S-morpholino stereocenter in 35% yield and a high-yielding (89%) Grignard reaction to generate the title compound la, isolated as a mesylate salt. The Grignard reaction was found to proceed optimally when using a combination of I2 and DIBAL-H for the initiation. In addition, the Grignard reagent formation was monitored by ReactMax calorimetry, and proof-of-concept studies were completed, demonstrating that the Grignard step could potentially be run as a continuous process with magnesium recycling.
MORPHOLINE DERIVATIVES AS NOREPINEPHRINE REUPTAKE INHIBITORS
-
Page/Page column 55-56, (2010/02/11)
Compounds of the general formula (I) are inhibitors of the reuptake of norepinephrine. As such, they may be useful for the treatment of disorders of the central and/or peripheral nervous system.
