Chloromethyl Methyl Ether → ethyl 3-tert-butyl-1-{4-[(methoxymethoxy)methyl]benzyl}-1H-pyrazole-5-carboxylate

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Reaction Steps

A mixed solution of ethyl 3-tert-butyl-1H-pyrazole-5-carboxylate (3.00 g, 15.3 mmol), [4-(chloromethyl)phenyl]methanol (2.50 g, 16.0 mmol), potassium carbonate (2.11 g, 15.3 mmol) and N,N-dimethylformamide (40 mL) was stirred at 70° C. for 3 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract washed with aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To a mixture of the obtained oil, N-ethyldiisopropylamine (8.00 mL, 45.9 mmol) and tetrahydrofuran (50 mL) was added dropwise a solution of chloromethyl methyl ether (4.40 mL, 46.3 mmol) in tetrahydrofuran (10 mL) at 0° C. The reaction mixture was stirred overnight at room temperature, and concentrated, and the obtained residue was subjected to silica gel chromatography (ethyl acetate:hexane=1:3) to give the title compound (1.95 g, yield 35%) as a colorless oil. 1H NMR (CDCl3) δ: 1.31 (1H, t, J=7.1 Hz), 1.32 (9H, s), 3.39 (3H, s), 4.26 (2H, q, J=7.1 Hz), 4.54 (2H, s), 4.68 (2H, s), 5.70 (2H, s), 6.71 (1H, s), 7.15-7.33 (4H, m).

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