Sodium hydride → HCID 19436795, compound

Participants

Reaction Conditions

Reaction Steps

6-[[1-Methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]oxy]-4-pyridazinol (Compound No. 12, 1.0 g, 0.0038 mole) and NaH (1.15 g of 80% NaH in oil, 0.0384 mole) were heated to 80° C. in DMF (20 mL) while CF2ClH was continuously bubbled through the solution for 6.5 h. The mixture was cooled to 0° C. and quenched by dropwise addition of water under an N2 sweep. After H2 ceased to evolve the mixture was poured into water/ethyl acetate and made acidic with excess ammonium chloride and then extracted 3×100 mL with ethyl acetate. The organic layers were extracted with brine, dried (MgSO4), filtered through silica gel with ethyl acetate, and evaporated in vacuo. Two compounds were present as evidenced by TLC. The mixture was separated by reverse phase chroma-tography to give 5-(difluoromethoxy)-3-[[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]oxy]pyridazine (0.144 g, 12% yield) as a yellow solid (mp= 86 -88° C.) and 5-ethoxy-3-[[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]oxy]pyridazine (0.058 g, 5% yield as a yellow solid.

Provenance & Evidence