Ethyl Acetate → 5-[4-(4-ethoxycarbonylmethyl-cyclohexyl)-phenyl]-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid benzyl ester

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Reaction Conditions

Reaction Steps

In another 2-neck 25 mL RB flask, palladium(II) acetate (18.1 mg, 0.081 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (66.2 mg, 0.162 mmol) were charged and the flask was purged with nitrogen gas. Then, THF (1 mL) was added and the resulting light brown suspension was stirred for 5 min before the addition of a solution of 5-(4-bromophenyl)-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid benzyl ester (120 mg, 0.322 mmol) in THF (3 mL) at room temperature under nitrogen atmosphere. Then, the above prepared colorless zinc solution was added to this mixture. During the addition, it turned to a brown solution which was then heated to 60° C. and stirred for 5 h at which time TLC analysis of the hydrolyzed reaction mixture indicated the absence of starting material. Then, it was cooled to room temperature and diluted with saturated ammonium chloride solution and ethyl acetate. The two layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine solution and dried over anhydrous MgSO4. Filtration of the drying agent and concentration of the filtrate gave the crude light yellow residue which was purified using an ISCO (80 g) column eluting with ethyl acetate in hexanes (0-100%). The desired fractions were combined and the solvent was removed under vacuum to obtain 5-[4-(4-ethoxycarbonylmethyl-cyclohexyl)-phenyl]-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid benzyl ester (55 mg, 37.0% yield) as a light brown oil. LC/MS calcd. for C27H31N3O4 (m/e) 461, obsd. 462.1 [M+H, ES+].

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