2867-59-6Relevant articles and documents
Substituent effects in the ring-chain tautomerism of 4-alkyl-2-aryl substituted oxazolidines and tetrahydro-1,3-oxazines
Juhasz, Marta,Lazar, Laszlo,Fueloep, Ferenc
, p. 1465 - 1473 (2007)
(Chemical Equation Presented) The condensation products of 2-aminoethanol or 3-aminopropanol (bearing an alkyl substituent on the carbon adjacent to the nitrogen) with substituted benzaldehydes proved to exist in CDCl3 at 300 K as three-component tautomeric mixtures of the diastereomeric five- or six-membered 1,3-O,N-heterocyclic ring forms and the corresponding imines. For each equilibrium, the electronic effects of the 2-aryl substituents were characterized by the Hammett equation. The steric effects of the alkyl groups could be described by Hansch-type equations for the equilibria involving oxazolidine ring forms. While the alkyl substituents did not cause any significant effect on the ring cis-chain and the ring trans-chain equilibria for tetrahydro-1,3-oxazines, increasing bulk of the 4-alkyl group increased the stability of the cyclic tautomers for the analogous oxazolidines.
Six-Step Gram-Scale Synthesis of the Human Immunodeficiency Virus Integrase Inhibitor Dolutegravir Sodium
Dietz, Jule-Philipp,Lucas, Tobias,Gro?, Jonathan,Seitel, Sebastian,Brauer, Jan,Ferenc, Dorota,Gupton, B. Frank,Opatz, Till
, p. 1898 - 1910 (2021/08/01)
A short and practical synthesis for preparing the active pharmaceutical ingredient dolutegravir sodium was developed. The convergent strategy starts from (R)-3-amino-1-butanol and establishes the BC ring system in a 76% isolated yield over four steps. Ring A was constructed by a one-pot 1,4-addition to diethyl-(2E/Z)-2-(ethoxymethylidene)-3-oxobutandioate and subsequent MgBr2·OEt2-mediated regioselective cyclization. Amide formation with 2,4-difluorobenzylamine was either performed from the free carboxylic acid or through aminolysis of the corresponding ethyl ester. Final salt formation afforded dolutegravir sodium in a 48-51% isolated yield (HPLC purity of 99.7-99.9%) over six linear steps.
Method for preparing (R)-3-aminobutanol
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Paragraph 0068-0077, (2020/01/25)
The invention provides a method for preparing (R)-3-aminobutanol, and the method comprises the following steps of: (1) providing 4-hydroxy-2-butanone and carrying out ammoniation reduction on the 4-hydroxy-2-butanone to obtain racemic 3-aminobutanol; (2) reacting (S)-mandelic acid with the racemic 3-aminobutanol to obtain resolved mandelic acid salt; and (3) alkalizing the resolved mandelic acid salt to obtain the product (R)-3-aminobutanol. According to the invention, the process of preparing the (R)-3-aminobutanol through reductive amination and salification resolution is simple and convenient to operate, low in reaction danger and pollution; the purity of the obtained (R)-3-aminobutanol reaches 99.9% (GC method).
Continuous Flow Synthesis of Morpholines and Oxazepanes with Silicon Amine Protocol (SLAP) Reagents and Lewis Acid Facilitated Photoredox Catalysis
Jackl, Moritz K.,Legnani, Luca,Morandi, Bill,Bode, Jeffrey W.
supporting information, p. 4696 - 4699 (2017/09/11)
Photocatalytic coupling of aldehydes and silicon amine protocol (SLAP) reagents enables the simple, scalable synthesis of substituted morpholines, oxazepanes, thiomorpholines, and thiazepanes under continuous flow conditions. Key to the success of this process is the combination of an inexpensive organic photocatalyst (TPP) and a Lewis acid additive, which form an amine radical cation that is easily reduced to complete the catalytic cycle. Di- and trisubstituted SLAP reagents are formed in one step by an iron-catalyzed aminoetherification of olefins.
