Reaktionsgleichung
[CH3:1][NH:2][CH2:3][CH2:4][C@H:5]([O:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=12)[C:6]1[S:10][CH:9]=[CH:8][CH:7]=1.[C:22](O)(=O)[C@H](C1C=CC=CC=1)O.CC1(C)O[C@H]2[C@@H]3OC(C)(C)O[C@]3(C(O)=O)O[C@H]2CO1.CN(C)CCC(C1SC=CC=1)O.FC1C2C(=CC=CC=2)C=CC=1>>[CH3:1][N:2]([CH3:22])[CH2:3][CH2:4][CH:5]([O:11][C:12]1[C:17]2[C:16](=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:15]=[CH:14][CH:13]=1)[C:6]1[S:10][CH:9]=[CH:8][CH:7]=1Komponenten
Versuchsvorschrift
The preparation of the enantiomerically pure duloxetine intermediate (S)-AT-OL by its chiral resolution is exemplified in U.S. Pat. No. 5,362,886 (U.S. '886) and in WO 2004/031168, by the use of (S)-(+)-mandelic acid and (−)-2,3:4,6-Di-O-isopropylidene-2-keto-L-gulonic acid, respectively. The U.S. '886 patent describes the preparation of duloxetine by the chiral resolution of N,N-Dimethyl-3-(2-thienyl)-3-hydroxypropanamine (rac-AT-OL) with (S)-mandelic acid (Stage a), its reaction with fluoronaphtalene (Stage b) to give N,N-Dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine (DNT), demethylation with phenyl chloroformate (Stage c), basic hydrolysis in the presence of (Stage d), and acidification (Stage e) in accordance with the following Scheme 1.
Quellen und Nachweise
- ORD-Eintrag
- ord-b4e13c2f94f946e48272c9a7635dea3d
- Quelldatensatz
- uspto-grants-2009_07
- Patentnummer
- US07560573B2
Verknüpfte Notizen
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