Hydrochloric Acid → 4-{5-(4-cyanophenyl)-2-methylbenzyl}-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 1.80 g (5.77 mmol) of 4-(5-bromo-2-methylbenzyl)-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the compound 299 of the present invention), 0.89 g (5.77 mmol) of 4-chlorobenzonitrile, 75 mg (0.577 mmol) of anhydrous nickel (II) chloride, and 0.31 g (1.15 mmol) of triphenylphosphine in 6 ml of pyridine was heated to 80° C. under an atmosphere of nitrogen. Then, 0.79 g (12.1 mmol) of zinc powder was added thereto, and the mixture was stirred at 80° C. under an atmosphere of nitrogen for 5 hours. After cooling to room temperature, the mixture was poured into a mixture of diluted hydrochloric acid (prepared by mixing 72 ml of water and 8 ml of concentrated hydrochloric acid) and ice, and ethyl acetate was added thereto. The resultant mixture was filtered with cotton and separated, and the organic layer was washed successively with an aqueous solution of sodium bicarbonate and water, then dried and concentrated. The residue (2.17 g) was subjected to silica gel column chromatography (eluted with hexane:ethyl acetate=2:1and then 1:1 for eluting impurities and then 1:2 for eluting the desired compound) to obtain 0.65 g of 4-{5-(4-cyanophenyl)-2-methylbenzyl}-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the compound 489 of the present invention) as crystals.

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