反应详情

温度

0 °C

A solution of 5-(2-trifluoromethyl-benzyl)-2H-pyridazin-3-one (219.6 mg, 0.86 mmol) in tetrahydrofuran (4.32 mL, 0.2M) cooled to 0° C. was treated with a 60% suspension of sodium hydride in mineral oil (41 mg, 1.03 mmol). The reaction stirred at 0° C. for 5 min and then at 25° C. for an additional 30 min. After this time, the reaction was treated with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10, 223 mg, 0.95 mmol). The reaction was then warmed to 50° C., where it stirred overnight. After this time, the reaction was diluted with water (150 mL) and methylene chloride (30 mL) and the resulting bilayer was extracted with methylene chloride (3×75 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 40 g, 25-40% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-benzyl)-6H-pyridazin-1-yl]-propionic acid methyl ester (155.9 mg, 44%) as a yellow oil; ES+-HRMS m/e calcd for C21H23N2O3F3 [M+H+] 409.1734, found 409.1733.

1. waitat 25° C. for an additional 30 min
2. temperatureThe reaction was then warmed to 50° C.
3. stirringwhere it stirred overnight
4. extractionthe resulting bilayer was extracted with methylene chloride (3×75 mL)
5. dry with materialThe combined organic layers were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo