Imidazole → 6-[(2RS,4SR)-2-(4-chlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethyloxy]-2-[3-(4-chlorophenyl)-propyl]-1,2,3,4-tetrahydroisoquinoline

Participants

Reaction Steps

550 mg of sodium hydride (50% suspension in oil) are added to a solution of 3.0 g of 6-hydroxy-2-[3-(4-chlorophenyl)propyl]-1,2,3,4-tetrahydroisoquinoline in 30 ml of dimethylacetamide, the mixture is stirred until evolution of hydrogen has ended, and 3.9 g of (2RS,4SR)-2-(4-chlorophenyl)-2-bromomethyl-1,3-dioxolan-4-ylmethyl methanesulfonate are added. The mixture is heated at 80° for 6 hours, and then 0.9 g of the sodium salt of imidazole and a spatula tip of potassium iodide are added. The solution is stirred at 100° for a further 6 hours. After cooling, the solvent is removed under oil pump vacuum, the residue is taken up with water/methylene chloride, and the organic phase is washed twice with water and dried over magnesium sulfate and the solvent is removed in vacuo. The crude product is purified by chromatography on silica gel using a mixture of ethyl acetate/methanol 9:1. 1.8 g of a viscous oil (31% of theory) which crystallizes on trituration with diethyl ether are obtained. Melting point: 101°-103°.

Provenance & Evidence