Methanol → (3R,4R)-methyl 4-(3-(6-methoxyquinolin-4-yl)-3-oxopropyl)piperidine-3-carboxylate
Reaktionsgleichung
[O:1]=[C:2]([C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][CH:22]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][C@@H:6]1[C:18](O)=[O:19].S(Cl)(Cl)=O.[CH3:37][OH:38]>>[O:1]=[C:2]([C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][CH:22]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][NH:8][CH2:7][C@@H:6]1[C:18]([O:38][CH3:37])=[O:19]Komponenten
4
Reaktionsbedingungen
- Temperatur
- -30 °C
Versuchsvorschrift
A solution of 19.4 g of (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-(t-butyloxycarbonyl)piperidine-3-carboxylic acid (80% content) in 355 cm3 of methanol is cooled to a temperature in the region of −30° C. Thionyl chloride (7.7 cm3)is added with stirring while maintaining the temperature between −25 and −30° C. After the addition, the mixture is maintained in the vicinity of −30° C. for 30 minutes and then the temperature is allowed to return to the vicinity of 20° C. After stirring at ambient temperature for 19 hours, the reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 30° C. The residue is taken up in 300 cm3 of water to which 200 cm3 of dichloromethane have been added, and then stirred. The organic phase is separated by settling; the aqueous phase is again extracted with 200 cm3 of dichloromethane. The aqueous solution is brought to pH 8 by gradual addition of solid sodium hydrogen carbonate. After extracting the alkaline solution 3 times with 200 cm3 of dichloromethane, the combined organic extracts are washed 2 times with 200 cm3 of water and then dried over magnesium sulfate. After filtering through a paper filter, the organic solution is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. to afford 4.51 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate.