Sodium Azide → 5-[1-(4-chloro-benzyl)-1H-[1,2,3]triazol-4-yl]-2-methyl-phenol

Participants

Reaction Conditions

Reaction Steps

To a suspension of 4-ethynyl-2-methoxymethoxy-1-methyl-benzene (1.50 g, 8.50 mmol) (from Example 19 supra), 4-chlorobenzyl bromide (1.76 g, 8.50 mmol) and sodium azide (0.56 g, 8.50 mmol) in a mixture of water (12 mL) and t-butanol (12 mL) was added copper powder (0.40 g, 6.30 mmol) and aqueous solution of copper sulphate solution (1 N, 1.64 mL). The reaction mixture was heated at 130° C. for 30 minutes in a microwave reactor. After cooling, the reaction mixture was partitioned between dichloromethane and water. The aqueous phase was extracted with dichloromethane (2×). The combined organic phase washed with water and brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography eluting with 40% ethyl acetate in hexanes to give 5-[1-(4-chloro-benzyl)-1H-[1,2,3]triazol-4-yl]-2-methyl-phenol; (Yield 0.75 g, 59%); and 1-(4-chloro-benzyl)-4-(3-methoxymethoxy-4-methyl-phenyl)-1H[1,2,3]triazole. (Yield 0.61 g, 21%).

Provenance & Evidence