868686-69-5Relevant articles and documents
Stereodivergent synthesis of all the four stereoisomers of antidepressant reboxetine
Liu, Cheng,Lin, Zhi-Wei,Zhou, Zhao-Hui,Chen, Hong-Bin
, p. 5395 - 5401 (2017/07/10)
Chiral amino alcohol-copper(ii) catalysts Cu-L1c and Cu-ent-L1c were utilized to promote the diastereoselective nitroaldol reactions of chiral aldehydes (S)-3 or (R)-3 with nitromethane, which respectively led to the preferential formation of certain stereoisomer for nitro diol derivatives 4. Using this catalytic protocol, all the four stereoisomers of the antidepressant reboxetine were divergently prepared. The highest overall yield of this synthetic route reached up to 30.5% from aldehyde (S)-3.
Dynamic kinetic resolution-based asymmetric transfer hydrogenation of 2-benzoylmorpholinones and its use in concise stereoselective synthesis of all four stereoisomers of the antidepressant reboxetine
Son, Se-Mi,Lee, Hyeon-Kyu
, p. 8396 - 8404 (2013/09/24)
Dynamic kinetic resolution-driven, asymmetric transfer hydrogenation reaction of 2-benzoylmorpholin-3-ones (4) proceeds efficiently to give the corresponding (2R,3S)- or (2S,3R)-2-(hydroxyphenylmethyl)morpholin-3-ones (6) with an excellent level of diastereo- and enantioselectivity and simultaneous control of two contiguous stereogenic centers in a single step. This process is employed to prepare all four stereoisomers of the antidepressant reboxetine.
Regioselective monochloro substitution in carbohydrates and non-sugar alcohols via Mitsunobu reaction: Applications in the synthesis of reboxetine
Dar, Abdul Rouf,Aga, Mushtaq A.,Kumar, Brijesh,Yousuf, Syed Khalid,Taneja, Subhash Chandra
, p. 6195 - 6207 (2013/09/12)
A regioselective high yielding monochloro substitution (chlorohydrin formation) via Mitsunobu reaction is reported. In carbohydrates and sterically hindered non-sugars, only the primary hydroxyl group is chlorinated, whereas in the non-sugar 1,2- and 1,3-alcohols, predominantly the secondary chloride substitution occurs. The versatile methodology provides indirect access to epoxides with the retention of configuration, as against conventional Mitsunobu reaction which generates epoxides with inversion. The methodology was successfully used as a key step in the synthesis of optically active diastereoisomers of the antidepressant drug reboxetine from (R)-2,3-O- cyclohexylidene-d-glyceraldehyde in ～43% overall yields. The Royal Society of Chemistry.
The synthesis of (R,S)-reboxetine employing a tandem cyclic sulfate rearrangement - Opening process
Yu, Jin,Ko, Soo Y.
, p. 650 - 654 (2012/09/22)
(R,S)-Reboxetine was synthesized in nine steps and with 43% overall yield starting from trans-cinnamyl alcohol. Following silylation and AD steps, the two hydroxyl groups at C-1 and C-2 were simultaneously activated to the cyclic sulfate. A series of tandem reactions initiated by desilylation transposed the activation to C-3, then to C-1, where nucleophilic displacements took place in succession. During this process, the configuration at C-2 was inverted while that at C-1 was retained through a double inversion.
Application of amide-stabilized sulfur ylide reactivity to the stereodivergent synthesis of (R,S)- and (S,R)-reboxetine
Aparicio, David M.,Teran, Joel L.,Gnecco, Dino,Galindo, Alberto,Juarez, Jorge R.,Orea, Maria L.,Mendoza, Angel
experimental part, p. 2764 - 2768 (2010/04/06)
A simple access to (R,S)- and (S,R)-reboxetine from a single chiral sulfonium salt 4 is reported. This approach, based on a stabilized sulfur ylide-mediated epoxidation, followed by a regioselective opening reaction, enables the preparation of these two p
Substituted morpholine compounds for the treatment of central nervous system disorders
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Page/Page column 51, (2010/02/14)
This invention relates to compounds of the formulae I wherein R1-R8, A, X, and Z are defined as in the specification, pharmaceutical compositions containing them and their use in the treatment of central nervous system disorders.
