Application of a process friendly morpholine synthesis to (S,S)-Reboxetine

Tetrahedron Letters

Volumn 51, Issue 38, 2010, Pages 5048-5051

  Assaf, Georges ^a   Cansell, Gemma ^a   Critcher, Doug ^a   Field, Stuart ^a   Hayes, Stewart ^a   Mathew, Suju ^a   Pettman, Alan ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL; AMINOALCOHOL; EPOXIDE; MORPHOLINE; REBOXETINE; WATER;

ALKYLATION; AMINATION; ARTICLE; CATALYSIS; CHEMICAL REACTION; DRUG SYNTHESIS; PROTON TRANSPORT;

EID: 78549248448     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2010.07.106     Document Type: Article

References (15)

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15. 2O (2 vol) and reslurried in EtOH (6 vol) to give 8 in 74% yield. Ring closure to 1: To a slurry of 8 (limiting reagent) in THF (7 vol) and EtOH (0.21 vol) at room temperature was added NaOH (3.0 equiv). The reaction mixture was heated to reflux for 3 h and cooled to room temperature. H2O (5 vol) and cyclohexane (4 vol) were added and the phases separated. The solvent was distilled and replaced with EtOH (5 vol) and succinic acid (1 equiv) was added to crystallize the product as the desired salt (82% yield).