Thionyl Chloride → 2-(3-Methoxy-4-methyl-phenyl)vinylisocyanate

Participants

Reaction Steps

3-(3-Methoxy-4-methylphenyl)propenoic acid (5.33 g, 27.7 mmol) (prepared according to the procedure described in J. Med. Chem. 1991, 34, 1662-1668) is suspended in benzene (30 mL) and treated dropwise with thionyl chloride (2.22 mL, 30.5 mmol) at 0° C. The reaction is heated to reflux and it is maintained for 1 hour. The volatiles are removed in vacuo and the resulting solid is dissolved in dioxane and added dropwise to a mixture of sodium azide (3.6 g, 55.4 mmol) in water/dioxane (30 mL, 1:5) at 0° C. After stirring 1 hours, the solution is poured over ice-water, the precipitate is collected and washed with water. The solid is dried under vacuum over P2O5(24 hours), dissolved in benzene (30 mL) and heated to reflux slowly over about 4 hours. The benzene is removed to give 2-(3-methoxy-4-methyl-phenyl)vinylisocyanate as a brown oil. The oil is taken tip in o-dichlorobenzene, treated with iodine and heated to reflux for 3.5 hours. The volatiles are removed and the residue is mixed with 2.5% MeOH/CH2Cl2 (10 mL), then allowed to stand overnight at room temperature. The resulting solid is collected washed with hexane and ether, and dried to give the title compound (2.67 g, 14.1 mmol).

Provenance & Evidence