Dichloromethane → HCID 73554912, compound

Temperature

2.5 °C

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.

1. additiontreated with urea hydrogen peroxide complex (4.0 g, 43 mmol)
2. temperatureto warm to 20° C.
3. stirringstirred for 20 h
4. stirringstirring
5. washThe organic phase was washed with H2O (10 mL)
6. dry with materialdried (Na2SO4)
7. customevaporated
8. dissolutionThis material was dissolved in phosphorus oxychloride (POCl3; 30 mL)
9. temperatureheated at 70° C. for 2 h
10. temperatureat reflux for 3 h
11. customto produce
12. temperatureAfter cooling
13. customthe volatiles were removed under vacuum
14. washThis solution was washed with H2O
15. dry with materialdried (Na2SO4)
16. customevaporated
17. customThe crude mixture was purified by reverse-phase high performance liquid chromatography (RP-HPLC; eluting with 60% acetonitrile (CH3CN)—H2O)

ORD record

ord-dee8c4f4ddf74a10900b01d7b798cdbb

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754229B2