Preparation method of 2-bromo-6-fluoronaphthalene

A technology of fluoronaphthalene and naphthylamine, which is applied in the field of pharmaceuticals, can solve problems such as equipment corrosion, seriousness, and harsh equipment requirements, and achieve the effect of simple routes

CN101870636AInactive Publication Date: 2010-10-27DATANGHANGZHOU PHARMACHEM
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2010-10-27
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention belongs to the technical field of pharmacy and relates to a preparation method of 2-bromo-6-fluoronaphthalene. In the method, tobias acid with low price is used as a starting material, and the 2-bromo-6-fluoronaphthalene as a target product is obtained through three steps of bromination-debromination, diazotization and thermal cracking and has high purity and stable quality. The synthesis process of the method only has three steps, thus the method has simple route, mild reaction condition and no need of high-pressure condition; and the fluoroboric acid which has low price and iseasy to obtain is used for generating a diazonium salt, thus the method has low cost and easy realization of industrialization.
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Description

technical field

[0001] The invention belongs to the technical field of pharmacy and relates to a preparation method of 2-bromo-6-fluoronaphthalene. Background technique

[0002] 2-Bromo-6-fluoronaphthalene is an intermediate for the synthesis of a class of niacin receptor competitive drugs. EP1809284 reported that this type of drug can be used to treat lipid abnormalities in patients with kidney disease, and can effectively reduce plasma low-density lipoprotein LDL, VLDL, At the same time, it increases the level of high-density lipoprotein HDL. Bioorganic & Medicinal Chemistry (2000), 8(8), 1925-1930 and (2005), 13(9), 3117-3126, Tetrahedron: Asymmetry (2002), 13(10), 1073-1081 and (2004), 15 (22), 3601-3608 reported a kind of pyrrole analgesics synthesized with 2-bromo-6-fluoronaphthalene as the basic raw material, which has a significant effect on the treatment of chronic pain. JP 2001019649 and EP 952135 (A1) reported a method for synthesizing liquid crystal active comp...

Examples

Embodiment 1

[0033] (1) Synthesis of 6-bromo-2-naphthylamine:

[0034] In a 2000ml three-necked flask equipped with a dropping funnel, a thermometer, a stirring device and a reflux condenser, add 1100ml of glacial acetic acid and 57.47g (0.25mol) of Turmeric's acid, start stirring, and heat to 70°C to dissolve the Turmeric's acid . 80 g (0.5 mol) of liquid bromine was added dropwise through the dropping funnel, and the temperature of the reactant was kept between 70-72° C. during the dropwise addition, and the dropwise addition was completed in about 1 hour. After the dropwise addition, the temperature was raised to reflux, and stirring was continued for 1.5 hours under reflux to complete the reaction. After the reaction finishes, the temperature of the reaction mixture is reduced to 65°C, adding 29.8g (0.251mol) metal tin powder and 340ml mass concentration is 35% hydrochloric acid, then the temperature of the reaction mixture is raised to reflux, and continues to stir for 2 Hour. Afte...

Embodiment 2

[0040] Carry out by the same method of embodiment 1, difference is that the thermal decomposition of the diazonium salt in the step (3) is carried out in the silicone oil that boiling point is in the range of 250-300 ℃, the product yield that obtains is 56.9%, HPLC The detection purity is 99.5%.

Embodiment 3

[0042] Carry out by the same method of embodiment 1, difference is, the thermal decomposition of the diazonium salt in the step (3) is carried out in liquid paraffin (C16-C20 normal alkanes), and the product yield that obtains is 58.4%, and HPLC detects 99.7% purity.