Category: esters-buliding-blocksIn 2021 ,《Process Development of a Second Generation β-Amyloid-Cleaving Enzyme Inhibitor-Improving the Robustness of a Halogen-Metal Exchange Using Continuous Stirred-Tank Reactors》 was published in Organic Process Research & Development. The article was written by Li, Bryan; Barnhart, Richard W.; Dion, Amelie; Guinness, Steven; Happe, Alan; Hayward, Cheryl M.; Kohrt, Jeffrey; Makowski, Teresa; Maloney, Mark; Nelson, Jade D.; Nematalla, Asaad; McWilliams, J. Christopher; Peng, Zhihui; Raggon, Jeffrey; Sagal, John; Weisenburger, Gerald A.; Bao, Denghui; Gonzalez, Miguel; Lu, Jiangping; McLaws, Mark D.; Tao, Jian; Wu, Baolin. The article contains the following contents:
Process development for the synthesis of a second generation β-amyloid-cleaving enzyme (BACE1) inhibitor is described. The lithiothiazole addition to the isoxazolene under batch conditions was not scalable because of reaction gelling and anion instability. A continuous stirred-tank reactor flow process was developed and successfully executed on the 70 kg scale in multiple runs. In a head-to-head comparison between the continuous and batch processes, the former was clearly superior as it gave a higher yield (80 vs 63%) of the (pyranoisoxazolyl)thiazole adduct and better reaction control for handling the unstable lithiothiazole as a reaction intermediate. Subsequently, (pyranoisoxazolyl)thiazole underwent Pd-catalyzed amination with t-Bu carbamate, reductive cleavage of the N-O bond, thioamidine cyclization, and deprotection of the Boc group to provide hydropyranothiazine. The synthesis of second generation β-amyloid-cleaving enzyme (BACE1) inhibitor was completed by amidation with 5-(difluoromethoxy)picolinic acid and the successive deprotection of the benzamide group with either Silicycle-diamine or L-lysine. In the part of experimental materials, we found many familiar compounds, such as tert-Butyl carbamate(cas: 4248-19-5Category: esters-buliding-blocks)
tert-Butyl carbamate(cas: 4248-19-5) belongs to anime. Halogenation, in which one or more hydrogen atoms of an amine is replaced by a halogen atom, occurs with chlorine, bromine, and iodine, as well as with some other reagents, notably hypochlorous acid (HClO). With primary amines the reaction proceeds in two stages, producing N-chloro- and N,N-dichloro-amines, RNHCl and RNCl2, respectively. With tertiary amines, an alkyl group may be displaced by a halogen.Category: esters-buliding-blocks
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics