Reacción #2286298

Ecuación de reacción

sodium acetate

[3,5-dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-proprionic acid

3-[3,5-Dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-propionic acid

→

[3,5-dibromo-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-proprionic acid

Rendimiento 72.0%

3-[3,5-Dibromo-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-propionic acid

Rendimiento 72.0%

Disolventes

acetic acid

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction mixture was cooled to room temperature
2. 2
   Concentraciónconcentrated
3. 3
   workup.ADDITIONThe resulting residue was diluted with water (200 mL)
4. 4
   workup.ADDITIONwas made basic to pH=9 by the addition of a 1N aqueous sodium hydroxide solution
5. 5
   ExtracciónThis solution was extracted with ethyl acetate (1×100 mL)
6. 6
   workup.ADDITIONThe water layer was acidified to pH=3 by the addition of a 1N aqueous hydrochloric acid solution
7. 7
   ExtracciónThe water layer was extracted with ethyl acetate (3×100 mL)
8. 8
   Secadodried with sodium sulfate
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated under vacuum
11. 11
    workup.ADDITIONHeptane (20 mL) was added to this mixture
12. 12
    ConcentraciónThe solvents were then concentrated under vacuum to a volume of approximately 20 mL
13. 13
    FiltraciónThe solids were filtered
14. 14
    Lavadowashed with a 1:1 ethyl acetate
15. 15
    OtroThe solid was dried under high vacuum

Procedimiento

A mixture of glacial acetic acid (16.7 mL), sodium acetate (480 mg, 5.85 mmol) and [3,5-dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-proprionic acid (22) (800 mg, 1.67 mmol) was heated to 120° C. for 24 h. The reaction mixture was cooled to room temperature and concentrated. The resulting residue was diluted with water (200 mL) and was made basic to pH=9 by the addition of a 1N aqueous sodium hydroxide solution. This solution was extracted with ethyl acetate (1×100 mL) and the ethyl acetate was discarded. The water layer was acidified to pH=3 by the addition of a 1N aqueous hydrochloric acid solution. The water layer was extracted with ethyl acetate (3×100 mL). The organic layers were combined, dried with sodium sulfate, filtered and concentrated under vacuum. The resulting solid was slurried in ethyl acetate (20 mL). Heptane (20 mL) was added to this mixture. The solvents were then concentrated under vacuum to a volume of approximately 20 mL. The solids were filtered and washed with a 1:1 ethyl acetate:heptane solution (2×10 mL). The solid was dried under high vacuum to afford [3,5-dibromo-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-proprionic acid (23) (553 mg, 72%) as an off-white solid; LRMS for C16H16Br2N2O4 (M+H) m/z=461. Molecular Weight=460.1249; Exact Mass=457.9477

Fuente