Reaktion #606989

Reaktionsgleichung

4′-{[4-(trans-4-hydroxycyclohexyl)-5-oxo-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

ethyl 2-diazopropanoate

Ethyl acetate

water

→

title compound

Ausbeute 84.0%

4′-({4-[trans-4-(2-hydroxy-1,2-dimethylpropoxy)cyclohexyl]-5-oxo-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile

Ausbeute 84.0%

Lösungsmittel

methylene chloride

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionthe mixture was extracted with ethyl acetate
2. 2
   WaschenThe organic layer was washed with water
3. 3
   Trocknenwith saturated brine, dried over anhydrous magnesium sulfate
4. 4
   Einengenconcentrated
5. 5
   SonstigeThe residue was crudely purified by silica gel column chromatography
6. 6
   workup.DISSOLUTIONThis was dissolved in tetrahydrofuran (5 mL)
7. 7
   workup.ADDITIONmethylmagnesium bromide (1 M tetrahydrofuran solution, 3 mL) was added dropwise at 0° C.
8. 8
   workup.STIRRINGthe mixture was stirred for 1 hr
9. 9
   workup.ADDITIONThe mixture was diluted with ethyl acetate
10. 10
    workup.ADDITIONsaturated aqueous ammonium chloride solution was added
11. 11
    ExtraktionThe mixture was extracted with ethyl acetate
12. 12
    Waschenthe organic layer was washed with saturated brine
13. 13
    Trocknendried over anhydrous magnesium sulfate
14. 14
    Einengenconcentrated
15. 15
    SonstigeThe residue was purified by silica gel column chromatography

Vorschrift

To a solution of 4′-{[4-(trans-4-hydroxycyclohexyl)-5-oxo-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.70 g) and rhodium acetate (dimer, 0.066 g) in methylene chloride (5 mL) was added dropwise a solution of ethyl 2-diazopropanoate (1.0 g) in methylene chloride (2 mL), and the mixture was stirred for 18 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was crudely purified by silica gel column chromatography. This was dissolved in tetrahydrofuran (5 mL), methylmagnesium bromide (1 M tetrahydrofuran solution, 3 mL) was added dropwise at 0° C., and the mixture was stirred for 1 hr. The mixture was diluted with ethyl acetate and then saturated aqueous ammonium chloride solution was added. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.45 g, 84%).

Quelle