4-Chloro-2-fluorobenzaldehyde → ethyl 4-((4-chloro-2-fluorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate

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Reaction Conditions

Reaction Steps

To a solution of ethyl 1-(2,4-dimethoxypyrimidin-5-yl)-4-iodo-5-isopropyl-1H-pyrazole-3-carboxylate (product from step 184.4, 1.15 g, 2.55 mmol) in 14 ml THF, a solution of 1M isopropylmagnesium chloride lithium chloride complex (2.68 ml, 2.68 mmol) was added at 0° C. and the mixture was stirred for 15 min. Then the solution was cooled down to −78° C. and a solution of 4-chloro-2-fluorobenzaldehyde (405 mg, 2.55 mmol) in 3 ml THF was added. The reaction mixture was stirred for 30 min at temperatures between −78° C. to −20° C. The solution was quenched with 10 ml of 1M NH4Cl solution, washed with brine and extracted 3 times with EtOAc. The combined organic phases were dried (Na2SO4), filtered and evaporated. The crude product was purified by chromatography (Silicagel, heptane, heptane/EtOAc 1:4) to give 977 mg (1.901 mmol, 74.5% yield) of the title compound as a white foam. LCMS: (M+H)=479; tR=1.18 min (LC-MS 4). HPLC: tR=5.48 min (HPLC 7). TLC: Rf=0.35 (Heptane/EtOAc 1:2).

Provenance & Evidence