Preparation method for montelukast sodium intermediate

[0028] A kind of preparation method of montelukast sodium intermediate of the present invention comprises following reaction process:

[0029]

[0030] Described reaction process comprises the following steps:

[0031] In the first step, the raw material methyl 2-(3-(3-bromophenyl)-3-oxopropyl)benzoate (II) is provided.

[0033] The preparation method of catalyst A comprises the following steps:

[0034] (1) After dissolving p-xylene with concentrated sulfuric acid at 0°C, add concentrated nitric acid dropwise, first react at this temperature for 1 hour, then raise the temperature to 100°C and continue the reaction for 2 hours. After the reaction is complete, introduce the reaction system into crushed ice , continue to stir to obtain a yellow solid;

[0035] (2) The yellow solid obtained in the step (1) was catalyzed by 10% Pd / C, stirred for 4 h under a hydrogen pressure of 1 atm, filtered off 10% Pd / C, and the reaction solution was concentrated to obtain a brownish-yellow oil;

[0036] (3) After dissolving the oil obtained in step (2) in dichloromethane, add it dropwise to Cbz-L-amino acid and CDI at 0°C, stir at room temperature for 2 hours, add water to quench, and wash the water layer with dichloromethane Extracted with methane, combined with dichloromethane, concentrated to give a light g...

[0041] A preparation method of montelukast sodium intermediate, comprising the following steps:

[0042] At first, in 100L autoclave, under the condition of communicating with argon gas, add raw material reactant 10kg methyl 2-(3-(3-bromophenyl)-3-oxopropyl group) methyl benzoate ( II), then add 60kg of toluene as a solvent to fully dissolve the raw material (II), continue to feed argon for bubbling and degassing, and continue bubbling for 1.5 hours; the degassing is completed. Under an argon atmosphere, add 2.5g of catalyst (R,R)-DIOPRuCl2(R)-Me-BIMAH from the feeding port, and finally add 150g of potassium tert-butoxide. After the addition, quickly close the feeding port.

[0043] Secondly, replace the argon with hydrogen, slowly introduce hydrogen to 35 atmospheres, then close the inflation valve, close the hydrogen channel, and finally stir, keep the reaction at 35°C, and the pressure will drop after starting to stir, observe the change of pressure, When the pressure rema...