| 摘要 |
PURPOSE: A method of preparing 3-(1-cyanoalkyl)benzoic acid, an important pharmaceutical intermediate to prepare anti-inflammatory drug Ketoprofen, using alkali metal salts 2-chlorobenzoate as a starting material is provided to prevent splash phenomenon of liquid ammonia caused by neutralization heat when 2-chlorobenzoic acid is directly added to liquid ammonia containing other raw materials. CONSTITUTION: The preparation method of 3-(1-cyanoalkyl)benzoic acid represented by the chemical formula 1 comprises the steps of (i) preparing alkali metal salts 2-chlorobenzoate represented by the chemical formula 2 (wherein R1 is hydrogen or C 1-C4 branched or straight chain alkyl group and M is Li, Na, K) by neutralizing 2-chlorobenzoic acid with alkali such as sodium hydroxide, potassium hydroxide in the equivalent ratio of 1:1 in a solvent such as water, methyl alcohol, ethyl alcohol, benzene, toluene, xylene in the temperature range of 25 to 100deg.C for 0.5-6hrs; (ii) reacting sodium amide/sodium and alkyl nitrile (R1CH2CN) in the temperature range of -35 to 30deg.C for 0.5hr at normal pressure to 7atm. in the liquid ammonia; (iii) adding alkali metal salts 2-chlorobenzoate prepared in the first step to resultant compound of the second step for 1.5hr as stirring, wherein other reacting conditions are the same as the second step; and then (iv) adding sequentially water and chloric acid to eliminate remaining sodium amide and filter out the solid products, 3-(1-cyanoalkyl)benzoic acid.
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