Preparation of methyl 4-iodo-3-methylbenzoate_Kain Industrial Additive

Background and overview^[1]

Methyl 4-iodo-3-methylbenzoate is an organic synthesis intermediate and pharmaceutical intermediate, which can be used in laboratory research and development processes and chemical and pharmaceutical research and development processes.

Preparation^[1]

Methyl 4-iodo-3-methylbenzoate is prepared as follows:

(a) 3-Methyl-4-iodobenzoic acid: 20g (0.132 mol) of 3-methyl-4-aminobenzoic acid and 175ml of sulfuric acid (20%) were introduced into a three-necked flask. At -10°C, a solution of 11.9g (0.172mol) sodium nitrite in 50ml water was added dropwise, and the mixture was stirred for 2 hours. This solution was added dropwise to 35 g (0.211 mol) of potassium iodide, 35.2 g (0.185 mol) of copper iodide and 175 ml of sulfuric acid (20%) through an ampoule chilled at -5°C. The mixture is stirred for eight hours, the reaction medium is filtered, the solid obtained is dissolved in ethyl acetate, washed with water and then with sodium sulfite solution, dried over magnesium sulfate and evaporated. Collected were 24.4 g (70%) of 3-methyl-4-iodobenzoic acid with a melting point of 205-10°C.

(b) Methyl 4-iodo-3-methylbenzoate: 24.4g (0.093 mol) 3-methyl-4-iodobenzoic acid and 250ml methanol were introduced into the flask, and 2.5ml concentrated sulfuric acid was added dropwise. The mixture is refluxed for twelve hours, the reaction medium is evaporated, the residue is taken up in ethyl acetate and water, the organic phase is decanted, dried over magnesium sulfate and evaporated. The residue was triturated in methanol and filtered, collecting 21.9 g (85%) of the desired methyl 4-iodo-3-methylbenzoate, melting point 58-9 °C.

Apply^[1]

Methyl 4-iodo-3-methylbenzoate can be used to prepare 3-methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 -Naphthylthio)benzoic acid: Make 2.4g (11mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylthiol and directly obtain 3g (11mmol) Methyl 4-iodo-3-methylbenzoate, 1.96g (51%) 3-methyl-4-(5,6,7,8-tetrahydro-5 acid), 5,8,8-tetramethyl (2-naphthylthio)benzoic acid, melting point 195-6°C.

Main reference materials

[1] EP0679630-BICYCLICAROMATICCOMPOUNDS,PHARMACEUTICALANDCOSMETICCOMPOSITIONSCONTAININGTHEMANDUSES