Propionic Acid → 3,6-Dichloro-4-ethylpyridazine

Temperature

60 °C

To a suspension of 3,6-dichloropyridazine (11.25 g, 0.076 mol, 1.0 eq), silver nitrate (6.41 g, 0.038 mol, 0.5 eq), propionic acid (8.39 g, 0.113 mol, 1.5 eq) in water (125 mL) at 50° C. was added a solution of sulfuric acid (11.54 mL, 0.227 ml. 3.0 eq) in water (125 mL). The solution was heated to 60° C. and then a solution of ammonium persulfate (51.7 g, 0.227 mol, 3.0 eq) was added in slowly in 20 minutes. The solution was then heated to 75° C. for 30 minutes. The reaction solution was poured into ice water and adjusted to pH 7 with 30% ammonium hydroxide solution. The mixture was extracted with dichloromethane (3×), and the extracts washed with water, brine, dried with sodium sulfate and concentrated in vacuo. The resulting residue was purified using an ISCO chromatography system (120 g silica cartridge, 5% ethyl acetate in heptane) to provide the compound 3,6-dichloro-4-ethylpyridazine (7.3 g, 54% yield). LC/MS, m/e 177.15 (M+1). HPLC Rt, 2.03 min. Waters Sunfire C18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

1. temperatureThe solution was then heated to 75° C. for 30 minutes
2. extractionThe mixture was extracted with dichloromethane (3×)
3. washthe extracts washed with water, brine
4. dry with materialdried with sodium sulfate
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified

ORD record

ord-ddf4c0e8c2b447c395fc63c463523450

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07723336B2