Reacción #494390

Ecuación de reacción

CH2Cl2

Methyl 6-chloro-3-methoxypicolinate

trifluoroacetic anhydride

sodium bisulfite

trifluoroacetic anhydride

→

title compound

Rendimiento 23.0%

methyl 4,6-dichloro-3-methoxypicolinate

Rendimiento 23.0%

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONtreated with urea hydrogen peroxide complex (4.0 g, 43 mmol)
2. 2
   Temperaturato warm to 20° C.
3. 3
   workup.STIRRINGstirred for 20 h
4. 4
   workup.STIRRINGstirring
5. 5
   LavadoThe organic phase was washed with H2O (10 mL)
6. 6
   Secadodried (Na2SO4)
7. 7
   Otroevaporated
8. 8
   workup.DISSOLUTIONThis material was dissolved in phosphorus oxychloride (POCl3; 30 mL)
9. 9
   Temperaturaheated at 70° C. for 2 h
10. 10
    Temperaturaat reflux for 3 h
11. 11
    Otroto produce
12. 12
    TemperaturaAfter cooling
13. 13
    Otrothe volatiles were removed under vacuum
14. 14
    LavadoThis solution was washed with H2O
15. 15
    Secadodried (Na2SO4)
16. 16
    Otroevaporated
17. 17
    OtroThe crude mixture was purified by reverse-phase high performance liquid chromatography (RP-HPLC; eluting with 60% acetonitrile (CH3CN)—H2O)

Procedimiento

Methyl 6-chloro-3-methoxypicolinate (prepared as in Van Heertum, J. C. et al. U.S. Pat. No. 5,571,775 A, Nov. 5, 1996; 4.0 g, 20 mmol) was dissolved in dry CH2Cl2 (20 mL), treated with urea hydrogen peroxide complex (4.0 g, 43 mmol), cooled to 0-5° C., stirred and treated in portions with trifluoroacetic anhydride (5.6 mL, 40 mmol). The mixture was allowed to warm to 20° C. and stirred for 20 h. An additional portion of the urea hydrogen peroxide complex (2.0 g) and trifluoroacetic anhydride (2.8 mL) were added and stirring was continued for 4 h. The mixture was stirred with 10% sodium bisulfite (NaHSO3) solution until negative to starch-iodide paper. The organic phase was washed with H2O (10 mL), dried (Na2SO4) and evaporated. This material was dissolved in phosphorus oxychloride (POCl3; 30 mL) and heated at 70° C. for 2 h and then at reflux for 3 h to produce a 1:1 mixture of the isomeric 4,5- and 4,6-dichloropicolinates. After cooling, the volatiles were removed under vacuum, the residue was combined with ice and the product was taken up in EtOAc. This solution was washed with H2O, dried (Na2SO4) and evaporated. The crude mixture was purified by reverse-phase high performance liquid chromatography (RP-HPLC; eluting with 60% acetonitrile (CH3CN)—H2O) to provide the title compound (1.1 g, 23%): 1H NMR (400 MHz, CDCl3) δ 7.50 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H); EIMS m/z 235.

Fuente