159112-23-9Relevant academic research and scientific papers
Telescoped Continuous Flow Synthesis of Optically Active γ-Nitrobutyric Acids as Key Intermediates of Baclofen, Phenibut, and Fluorophenibut
?tv?s, Sándor B.,Kappe, C. Oliver,Llanes, Patricia,Pericàs, Miquel A.
supporting information, p. 8122 - 8126 (2020/11/03)
The two-step flow asymmetric synthesis of chiral γ-nitrobutyric acids as key intermediates of the GABA analogues baclofen, phenibut, and fluorophenibut is reported on a multigram scale. The telescoped process comprises an enantioselective Michael-type add
Chemical assembly systems: Layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients
Ghislieri, Diego,Gilmore, Kerry,Seeberger, Peter H.
supporting information, p. 678 - 682 (2015/03/04)
While continuous chemical processes have attracted both academic and industrial interest, virtually all active pharmaceutical ingredients (APIs) are still produced by using multiple distinct batch processes. To date, methods for the divergent multistep continuous production of customizable small molecules are not available. A chemical assembly system was developed, in which flow-reaction modules are linked together in an interchangeable fashion to give access to a wide breadth of chemical space. Control at three different levels - choice of starting material, reagent, or order of reaction modules - enables the synthesis of five APIs that represent three different structural classes (γ-amino acids, γ-lactams, β-amino acids), including the blockbuster drugs Lyrica and Gabapentin, in good overall yields (49-75%).
Water-compatible iminium activation: Organocatalytic Michael reactions of carbon-centered nucleophiles with enals
Palomo, Claudio,Landa, Aitor,Mielgo, Antonia,Oiarbide, Mikel,Puente, Angel,Vera, Silvia
, p. 8431 - 8435 (2008/09/19)
(Chemical Equation Presented) A pool of water-compatible catalysts, namely the chiral prolinol-based catalysts 1, has been developed for highly enantioselective C-C bond-forming Michael reactions in water (see scheme). The synthesis of (S)-Rolipram, a type IV phosphodiesterase inhibitor, was also demonstrated.
Synthesis of both enantiomers of baclofen using (R)- and (S)-N-phenylpantolactam as chiral auxiliaries
Camps, Pelayo,Munoz-Torrero, Diego,Sanchez, Laura
, p. 2039 - 2044 (2007/10/03)
Esterification of racemic 4-nitro-3-(4-chlorophenyl)butanoic acid with (R)- or (S)-N-phenylpantolactam as the chiral auxiliary allowed us to obtain the (3R,3′R)- or (3S,3′S)-nitro esters with >98:2 dr after column chromatography. Hydrolysis of the resulti
Potential GABAB Receptor Antagonists. VII. The Synthesis of 2-(4-Chlorophenyl)-3-nitropropan-1-amine and Related Analogues of Baclofen
Abbenante, Giovanni,Hughes, Robert,Prager, Rolf H.
, p. 1441 - 1452 (2007/10/02)
3-Nitro-2-phenylpropan-1-amine and 2-(4-chlorophenyl)-3-nitropropan-1-amine have been synthesized by the addition of nitrous acid to the corresponding trifluoroacetylaminomethylstyrenes followed by reduction of the double bond with sodium borohydride.A more general and efficient route involves the Michael addition of nitroalkane anions to methyl cinnamates followed by Curtius degradation of the corresponding acids. 2-(4-Chlorophenyl)-3-nitropropan-1-amine is a specific agonist of GABA and the GABAB receptor, with about half the activity of racemic baclofen at the isolated guinea pig ileum.Methylation or dimethylation at C3 decreases activity markedly.
