Reaction #1509596

Reaction equation

2-Chloro-N-hydroxy-6-methyl-isonicotinamidine

acetic acid

→

title compound

2-Chloro-6-methyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-pyridine

Solvents

trimethylorthoacetate

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   TemperatureAfter cooling to room temperature the solvent
3. 3
   Otherwas evaporated under reduced pressure
4. 4
   Otherthe residue partitioned between EtOAc and aqueous solution of NaHCO3
5. 5
   OtherThe organic layer was separated
6. 6
   Washwashed with water and brine
7. 7
   Otherdried under Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Otherthe solvent was evaporated under reduced pressure
10. 10
    OtherThe crude was purified by flash column chromatography (10 g Isolute® silica gel cartridge; gradient elution: hexane/EtOAc from 10/0 to 9/1)

Procedure

2-Chloro-N-hydroxy-6-methyl-isonicotinamidine (120 mg) was suspended in trimethylorthoacetate (3 ml) under inert atmosphere and acetic acid (0.3 ml) was added. The mixture was heated to 100° C. and stirred for 2 h. After cooling to room temperature the solvent was evaporated under reduced pressure and the residue partitioned between EtOAc and aqueous solution of NaHCO3. The organic layer was separated, washed with water and brine, dried under Na2SO4, filtered and the solvent was evaporated under reduced pressure. The crude was purified by flash column chromatography (10 g Isolute® silica gel cartridge; gradient elution: hexane/EtOAc from 10/0 to 9/1) affording the title compound (107 mg).

Source