100791-85-3Relevant articles and documents
Chiral synthesis method of ephedrine key intermediate (S)-2-methylamino-1-phenyl-1-acetone
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, (2021/04/14)
The invention discloses a chiral synthesis method of an ephedrine key intermediate (S)-2-methylamino-1-phenyl-1-acetone. The method comprises the following steps: carrying out nucleophilic substitution reaction on dimethyl-(4S, 5S)-2-[(R)-1-bromoethyl]-2-phenyl-1, 3-dioxyethane-4, 5-dicarboxylate (2a) and methylamine in an SN2 reaction environment to finish Walden inversion to generate dimethyl-(4S, 5S)-2-[(S)-1-methylamino]-2-phenyl-1, 3-dioxyethane-4, 5-dicarboxylate(3a); and then removing a chiral auxiliary agent (2S, 3S)-dimethyl tartrate to obtain (S)-2-methylamino-1-phenyl-1-acetone (1a). The compound can be used as a substrate for potassium borohydride reduction in the ephedrine preparation process, so that traditional complicated physical and chemical coexisting splitting operation of dibenzoyl tartaric acid is avoided, and the method has an important industrial application value.
Novel Preparation of α,β-Unsaturated Aldehydes. Benzeneselenolate Promotes Elimination of HBr from α-Bromoacetals
Vasil'ev, Andrei,Engman, Lars
, p. 2151 - 2162 (2007/10/03)
Acetalization, α-bromination, nucleophilic phenylselenenylation, oxidative elimination/hydrolysis was investigated as a novel protocol for the α,β-dehydrogenation of aldehydes. Treatment of acetals with bromine in methylene chloride afforded the corresponding α-bromoacetals in 80-90% yields. Nucleophilic phenylselenenylation was then conveniently effected by treatment with benzenese-lenolate generated in situ in dimethyl sulfoxide from diphenyl diselenide, hydrazine and potassium carbonate. Unbranched α-bromoacetals cleanly afforded substitution products whereas β- and γ-branched ones gave substantial amounts of α,β-unsaturated acetals via formal loss of hydrogen bromide. Oxidative elimination/hydrolysis of these mixtures afforded α,β-unsaturated aldehydes in 50-80% overall yields. In the case of tertiary α-bromoacetals, treatment with benzeneselenolate afforded only dehydrobromination products as mixtures of isomers. The presence of at least a catalytic amount of the organoselenium reagent was found to be crucial for olefin formation. A SET-mechanism, involving benzeneselenolate-induced electron transfer to the halide, loss of bromide ion, and hydrogen atom or proton/electron was proposed for the benzenselenolate-promoted elimination reaction. Experiments designed to trap carbon-centered radicals in intramolecular cyclization or ring-opening reactions failed to provide any evidence for free-radical intermediates.
Tartaric Acid, an Efficient Chiral Auxiliary: New Asymmetric Synthesis of 2-Alkyl-2-arylacetic Acids
Castaldi, Graziano,Cavicchioli, Silvia,Giordano, Claudio,Uggeri, Fulvio
, p. 3018 - 3027 (2007/10/02)
A highly enantioselective synthesis of 2-alkyl-2-arylacetic acids, an important class of antiinflammatory agents, based on a new diastereoselective α-bromination of homochiral acetals 1 and on the stereospecific silver-promoted rearrangement of the corresponding homochiral α-bromo acetals 2 and 3, is reported.The new methodology represents a meaningful example of the use of tartaric acid as efficient and economic chiral auxiliary.The asymmetric bromination of 1 is of general character and occurs with very high diastereoselectivity, even at room temperature; a mechanism for the new reaction is proposed.The overall process has been successfully applied to the preparation of enantiomerically pure 2-alkyl-2-arylacetic acids, among them (2S)-(+)-2-(6-methoxy-2-naphthyl)propanoic acid (Naproxen)
