26307-50-6Relevant articles and documents
Desymmetric enantioselective reduction of cyclic 1,3-diketones catalyzed by a recyclable p-chiral phosphinamide organocatalyst
Qin, Xu-Long,Li, Ang,Han, Fu-She
supporting information, p. 2994 - 3002 (2021/03/01)
The P-stereogenic phosphinamides are a structurally novel skeletal class which has not been investigated as chiral organocatalysts. However, chiral cyclic 3-hydroxy ketones are widely used as building blocks in the synthesis of natural products and bioactive compounds. However, general and practical methods for the synthesis of such chiral compounds remain underdeveloped. Herein, we demonstrate that the P-stereogenic phosphinamides are powerful organocatalysts for the desymmetric enantioselective reduction of cyclic 1,3-diketones, providing a useful method for the synthesis of chiral cyclic 3-hydroxy ketones. The protocol displays a broad substrate scope that is amenable to a series of cyclic 2,2-disubstituted five- and six-membered 1,3-diketones. The chiral cyclic 3-hydroxy ketone products bearing an all-carbon chiral quaternary center could be obtained with high enantioselectivities (up to 98% ee) and diastereoselectivities (up to 99:1 dr). Most importantly, the reactions could be practically performed on the gram scale and the catalysts could be reused without compromising the catalytic efficiency. Mechanistic studies revealed that an intermediate formed from P-stereogenic phosphinamide and catecholborane is the real catalytically active species. The results disclosed herein bode well for designing and developing other reactions using P-stereogenic phosphinamides as new organocatalysts.
Development of a green and sustainable manufacturing process for gefapixant citrate (MK-7264) Part 2: Development of a robust process for phenol synthesis
Peng, Feng,Humphrey, Guy R.,Maloney, Kevin M.,Lehnherr, Dan,Weisel, Mark,Lévesque, Francois,Naber, John R.,Brunskill, Andrew P.J.,Larpent, Patrick,Zhang, Si-Wei,Lee, Alfred Y.,Arvary, Rebecca A.,Lee, Claire H.,Bishara, Daniel,Narsimhan, Karthik,Sirota, Eric,Whittington, Michael
, p. 2453 - 2461 (2020/11/18)
Various synthetic routes to 2-isopropyl-4-methoxyphenol 3, the phenol core of Gefapixant citrate (MK-7264), are described, which provide better alternatives to the initial four-step supply route. These new routes include a coumarin fragmentation approach in flow, a rhenium-catalyzed isopropylation of mequinol, and a bromination/methoxylation of 2-isopropylphenol. After exploring several approaches, a robust two-step process for the preparation of 3 from the commodity starting material 2-isopropylphenol was developed. The optimized route employs a highly regioselective bromination. After isolating the bromophenol DABCO cocrystal, a copper-catalyzed methoxylation delivers 3 in high yield. This route is successfully demonstrated at the plant scale with low process mass intensity and cost.
Chasing the Elusive Benzofuran Impurity of the THR Antagonist NH-3: Synthesis, Isotope Labeling, and Biological Activity
Singh, Latika,Pressly, Brandon,Mengeling, Brenda J.,Fettinger, James C.,Furlow, J. David,Lein, Pamela J.,Wulff, Heike,Singh, Vikrant
, p. 1870 - 1876 (2016/03/15)
We have synthesized and established the structure of a long-suspected, but hitherto unknown, benzofuran side product (EBI) formed during the synthesis of NH-3. Understanding the mechanism of its formation has enabled isotope (D) labeling. We further devel