Reaktion #8404

Reaktionsgleichung

4-(4-methyl-piperazin-1-ylmethyl)-benzonitrile

5-methyl-3-phenyl-isoxazole-4-carboxylic acid methylamide

butyl lithium

→

5-methyl-6-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-phenyl-5H-isoxazolo[4,5-c]pyridin-4-one

Ausbeute 41.2%

Lösungsmittel

THF

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturUnder warming to room temperature
2. 2
   Sonstigequenched with 2 ml of water
3. 3
   Einengenconcentrated
4. 4
   Sonstigekept at 5° C
5. 5
   workup.ADDITIONThen, 230 ml of a 4M solution of HCl in dioxane is carefully added
6. 6
   workup.STIRRINGthe suspension stirred for 20 h at room temperature
7. 7
   SonstigeThen, the solvent is removed
8. 8
   workup.DISSOLUTIONthe residue dissolved in ethyl acetate
9. 9
   SonstigeThe phases are separated
10. 10
    Waschenthe organic phases washed with brine
11. 11
    Trocknendried over Na2SO4
12. 12
    Einengenconcentrated
13. 13
    SonstigeChromatographic purification (CH2Cl2/MeOH 95:5 to 90:10)

Vorschrift

In a 500 ml flask, 10.0 g (46.3 mmol) of 5-methyl-3-phenyl-isoxazole-4-carboxylic acid methylamide is suspended in 150 ml of tetrahydrofuran (THF) under argon. At −70° C. a solution of butyl lithium (63 ml, 1.6M in hexane, 101 mmol, 2.2 eq.) is slowly added. After 1 h at this temperature, the solution is warmed to −10° C. and a solution of 11.9 g (55.5 mmol, 1.2 eq.) of 4-(4-methyl-piperazin-1-ylmethyl)-benzonitrile in 80 ml of THF is slowly added. Under warming to room temperature, the red solution is stirred for another hour, then quenched with 2 ml of water and concentrated. The yellow residue is then taken up in 75 ml of dioxane and kept at 5° C. Then, 230 ml of a 4M solution of HCl in dioxane is carefully added and the suspension stirred for 20 h at room temperature. Then, the solvent is removed and the residue dissolved in ethyl acetate and carefully neutralised with sat. NaHCO3-solution. The phases are separated and the organic phases washed with brine, dried over Na2SO4 and concentrated. Chromatographic purification (CH2Cl2/MeOH 95:5 to 90:10) yields 7.9 g (41%) of 5-methyl-6-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-phenyl-5H-isoxazolo[4,5-c]pyridin-4-one as a white solid. Mass spectrum: m/z (M+H)+: 415.0

Quelle