5-[4-(4-METHOXYPHENOXY)PHENYL!-1H-PYRAZOLE, 97 synthesis

Yield:620633-54-7 43%

Reaction Conditions:

with hydrazine hydrochloride in methanol;water at 20;

Steps:

67.B

Part B: 3-[4-(4-Methoxy-phenoxy)-phenyl]-1H-pyrazole 1-[4-(4-Methoxy-phenoxy)-phenyl]-ethanone (1.89 g, 7.8 mmol) and ethyl formate (1 mL, 11.7 mmol) were added to a flame dry flask and dissolved in toluene (13 mL), and stirred under N₂. Sodium methoxide (420 mg, 7.8 mmol) was added to a separate flame dry flask, and toluene (41 mL) was added to produce a slurry which was stirred under N₂. The solution of ketone and ethyl formate was added to the sodium methoxide slurry in one portion by syringe, and the resulting mixture was stirred for 1.5 hours at room temperature. The slurry which formed was filtered and rinsed with hexanes. The solid was dissolved in 20 ml methanol. Hydrazine hydrochloride (538 mg, 7.8 mmol) was dissolved in 15 ml H₂O and added dropwise to the methanol solution, a color change to bright yellow was observed, and the resulting mixture was stirred overnight at room temperature. Water was added and the solution was extracted with methylene chloride, washed with water and brine, dried over sodium sulfate, filtered, and concentrated under vacuum to provide 1.03 g of crude product. ISCO MPLC purification (30 minutes run, 0-50% EtOAC gradient, Biotage flash 40s column) gave 900 mg of the title compound (43%). MS m/z: APCI+267 (M+H)⁺, APCI-266 (M)^-.

References:

US2004/6057,2004,A1 Location in patent:Page/Page column 38