反应详情

温度

0 °C

A solution of 4′-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-5-fluoro-6-methyl-1,1′-biphenyl-3-carboxamide (Example 45) (96 mg) in acetic acid/water (1:1 v/v, 7 ml) was cooled to 0° C. Sodium nitrite (206 mg) was added and the solution stirred for 30 minutes at 0° C. and then for a further 16 hours at room temperature. Concentrated sodium hydroxide solution (10 ml) was added to the reaction and the mixture extracted with ether (3×40 ml) and then chloroform (40 ml). The organic phases were combined, dried and reduced to dryness under vacuum. The residue was dissolved in 5% potassium hydroxide in methanol and stirred at room temperature for 90 minutes. The methanol was removed in vacuo, the residue partitioned between ethyl acetate/chloroform (1:1)/water and the organic phase dried and reduced to dryness under vacuum. This material was purified by chromatography on a bond-elut (silica, 2 g), eluting with an ethyl acetate/cyclohexane gradient to give after evaporation of the solvent N-cyclopropyl-5-fluoro-4′-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]-6-methyl-1,1′-biphenyl-3-carboxamide.

1. waitfor a further 16 hours at room temperature
2. extractionthe mixture extracted with ether (3×40 ml)
3. customdried
4. dissolutionThe residue was dissolved in 5% potassium hydroxide in methanol
5. stirringstirred at room temperature for 90 minutes
6. customThe methanol was removed in vacuo
7. customthe residue partitioned between ethyl acetate/chloroform (1:1)/water
8. customthe organic phase dried
9. customThis material was purified by chromatography on a bond-elut (silica, 2 g)
10. washeluting with an ethyl acetate/cyclohexane gradient
11. customto give
12. customafter evaporation of the solvent N-cyclopropyl-5-fluoro-4′-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]-6-methyl-1,1′-biphenyl-3-carboxamide