1,10-Phenanthroline → HCID 86675407, compound

Temperature

65 °C

To a dry 1 liter (L) flask was added methyl 4-amino-6-chloro-5-fluoro-3-iodopicolinate (50 g, 151 mmol) and cesium carbonate (Cs2CO3; 99 g, 303 mmol). CH3OH (378 mL) was added, and the solution was sparged with nitrogen for 10 min. 1,10-Phenanthroline (6.00 g, 30.3 mmol) and copper(I) iodide (CuI; 2.88 g, 15.13 mmol) were added, and the flask was fitted with a reflux condenser and heated to 65° C. under nitrogen. After 12 h, CuI (2.88 g, 15.13 mmol) was again added to the reaction mixture, and heating was continued until consumption of the iodopicolinate was observed. The reaction mixture was cooled to room temperature, filtered through Celite, and concentrated in vacuo. To the crude residue was added EtOAc (100 mL) and H2O (100 mL). The layers were separated, and the aqueous phase was acidified to pH=2 with concentrated (conc) HCl and subsequently extracted with EtOAc (3×100 mL). The organic extracts were combined, washed with satd aq NaCl, dried (Na2SO4), filtered, and concentrated in vacuo to afford 4-amino-6-chloro-5-fluoro-3-methoxypicolinic acid.

1. customthe solution was sparged with nitrogen for 10 min
2. customthe flask was fitted with a reflux condenser
3. temperatureheating
4. customwas continued until consumption of the iodopicolinate
5. temperatureThe reaction mixture was cooled to room temperature
6. filtrationfiltered through Celite
7. concentrationconcentrated in vacuo
8. additionTo the crude residue was added EtOAc (100 mL) and H2O (100 mL)
9. customThe layers were separated
10. concentrationwith concentrated (conc) HCl
11. extractionsubsequently extracted with EtOAc (3×100 mL)
12. washwashed with satd aq NaCl
13. dry with materialdried (Na2SO4)
14. filtrationfiltered
15. concentrationconcentrated in vacuo

ORD record

ord-bd8262ffb7544558a1518fe2228aec94

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754229B2