Iodine → HCID 58079360, compound

Participants

Reaction Steps

Magnesium turnings (8.5 g, 0.35 mol) are activated by stirring at room temperature overnight under argon and suspended in anhydrous tetrahydrofuran (60 ml). 10 ml of a solution of 3,5-dimethoxychlorobenzene (60.4 g, 0.35 mol) in anhydrous tetrahydrofuran (75 mL) is added, followed by a crystal of iodine, and the mixture is placed in an ultrasonic bath for 10 minutes. A further 10 mL of the solution of 3,5-dimethoxychlorobenzene in tetrahydrofuran is added and reaction is heated at 80° C. for 1 h. The remainder of the starting material is added dropwise to the reaction mixture at 80° C. over 50 minutes, then heating is continued at 80° C. for a further 30 minutes. The reaction mixture is cooled to below room temperature in an ice/water bath and a solution of tetrahydrofuran-3-carbaldehyde (35 g, 0.35 mol) in anhydrous tetrahydrofuran (35 mL) is added dropwise over 30 minutes. Once the addition is complete, the reaction mixture is stirred at room temperature overnight. The reaction mixture is decanted and 2M aqueous hydrochloric acid is carefully added to the decanted solution, until the pH of the reaction mixture reaches pH 1. The reaction mixture is extracted with ethyl acetate (4×100 mL) and the organic extracts are combined, washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. The residue is purified by column chromatography on silica gel to give (3,5-dimethoxyphenyl)(tetrahydrofuran-3-yl)methanol as a yellow oil.

Provenance & Evidence