Mix 2.87 g (19 mmol) in a 50 ml flask of 1-bromopentane in 20 ml of diethyl ether, previously distilled over sodium, and 0.4 g (17 mmol) of magnesium powder. The flask is heated in a water bath until the ether begins to boil (use long Liebig reflux condenser), then the heating is removed because the reaction is exothermic. The reaction takes 15-20 minutes, after the Grignard reagent mixture is refluxed for 30 minutes.
Then the reaction mixture is cooled to 0°С, transferred to a 250 ml flask, and 1.8 g (16 mmol; 1 eq.) of slightly yellowish indole in 20 ml of dichloromethane is added. Gas is released in the form of bubbles during this reaction, the mixture remains transparent, use a reflux condenser.
To the same flask is added 1.63 g (15 mmol) of anhydrous ZnCl2 (in the form of a crushed powder). At the same time, gas and bubbles are actively released, the mixture becomes dull, the color changes to pink or greenish. The reaction mixture is stirred for 40 minutes. Next, a solution of 3.7 g (19 mmol) of 1-naphthoyl chloride dissolved in 30 ml of dichloromethane is added. The reaction mixture instantly changes color to red, the product immediately precipitates in the form of a thick paste. The mixture is stirred for an additional 1 hour at r.t., then diluted with an equal volume of 30% NH4Cl aq. and mixture is stirred few minutes.
Water and solvent are decanted, 10 ml of methanol is added to the precipitate and triturated with a glass rod, while small yellowish crystals are precipitated. The crystals are filtered, washed with 10 ml of methanol and 7 ml of diethyl ether. The mass of dry pale yellow dusty powder of JWH-018 is 2.93g (64%). An additional 200-400 mg of the product can be obtained from the filtered liquors.
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