Reaktion #677133

Reaktionsgleichung

EtMgBr

4-benzyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester

EtMgBr

→

title compound

Ausbeute 58.0%

4-benzyl-4,7-diaza-spiro[2.5]octane-7-carboxylic acid tert-butyl ester

Ausbeute 58.0%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe resultant reaction mixture
2. 2
   Temperaturwas heated
3. 3
   Temperaturto reflux for 1 h
4. 4
   SonstigeThe reaction mixture was quenched with NH4Cl solution
5. 5
   workup.STIRRINGstirred for 15 min
6. 6
   Filtrationfiltered through a celite bed
7. 7
   Waschenwashed with EtOAc
8. 8
   ExtraktionThe aqueous layer was again extracted with EtOAc (3×)
9. 9
   WaschenThe combined EtOAc layers were washed with water
10. 10
    Trocknendried over Na2SO4
11. 11
    Einengenconcentrated under reduced pressure
12. 12
    SonstigePurification by column chromatography

Vorschrift

To EtMgBr (344 mL) in THF cooled to −78° C. was added Ti(OiPr)4 (39 g, 137.93 mmol), followed by commercially available 4-benzyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (40 g, 137.93 mmol) and the resultant reaction mixture was heated to reflux for 1 h. After cooling the reaction mixture to 5° C., another portion of EtMgBr (344 ml) and Ti(OiPr)4 (39 g, 137.93 mmol) was added. The mixture was stirred for 16 h at RT. The reaction mixture was quenched with NH4Cl solution and stirred for 15 min and filtered through a celite bed and washed with EtOAc. The aqueous layer was again extracted with EtOAc (3×). The combined EtOAc layers were washed with water and dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography to afforded the title compound as a solid (24 g, 58%).

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