CN-121060413-B - Synthetic candesartan apparatus for tam intermediates

Abstract

The invention relates to the technical field of candesartan intermediate synthesis, in particular to equipment for synthesizing candesartan intermediate, which comprises a micro-channel reactor, a tubular reactor and a continuous separator, wherein the tubular reactor also comprises an outer tube and a mixer arranged in the outer tube, the mixer comprises a tube body and an SK core piece, the SK core piece is formed by combining a plurality of spiral slices which are twisted by 180 degrees left and right, a liquid inlet and a liquid outlet are formed in the surface of the outer tube, and the equipment is convenient for a user to independently detach and clean or replace the blocked SK core piece by arranging the SK core piece, does not need to integrally replace an expensive SK type static mixer, greatly reduces equipment purchase cost, also does not need to integrally detach and reload the tubular reactor, remarkably reduces the downtime, and further improves the integral production efficiency of the candesartan intermediate.

Inventors

• YANG HAO
• ZHANG HONGDUO
• ZHU SHIYUAN
• ZHANG YI
• HU ZAIXIAN

Assignees

• 滨海三甬药业化学有限公司

Dates

Publication Date

20260508

Application Date

20250811

Claims (3)

1. 1. A device for synthesizing candesartan intermediate comprises a microchannel reactor, a tubular reactor and a continuous separator, wherein the tubular reactor further comprises an outer tube (1) and a mixer (2) arranged inside the outer tube (1), the mixer (2) comprises a tube body (21) and an SK core piece (22), the SK core piece (22) is formed by combining a plurality of spiral pieces (221) which are twisted by 180 DEG left and right, a liquid inlet (11) and a liquid outlet (12) are formed on the surface of the outer tube (1), the device is characterized in that a first flange (211) and a second flange (212) are respectively arranged at two ends of the tube body (21), bolt holes (213) are formed on the surfaces of the first flange (211) and the second flange (212), threaded holes (13) which are opposite to the bolt holes (213) are formed at two ends of the outer tube (1), the first flange (211) is fixedly connected with the tube body (21), the second flange (212) is in threaded connection with the tube body (21), a liquid inlet (11) and a liquid outlet (12) are formed on the surface of the outer tube (1), a first flange (211) and a second flange (23) is fixedly connected with the tube (21), one end of the second flange (21) is fixedly connected with the other end (23) of the second flange (23) is fixedly connected with the second flange (21), and the second flange (23) is fixedly connected with the first flange (21) and the second flange (23) is fixedly connected with the second flange (22) The fixing unit is used for fixing the SK chip in the pipe body (21); The fixing unit comprises a fixing groove (214), wherein the fixing groove (214) is formed in the inner wall of the pipe body (21), a fixing block (215) is connected in a sliding and sealing mode in the fixing groove (214), a connecting groove (216) is formed in the lower end of the fixing block (215), a positioning groove (242) matched with the fixing block (215) is formed in the upper end of the clamping block (24), a groove (25) communicated with the fixing groove (214) is formed in the surface of the first flange (211), and a screw rod (251) is connected to the groove (25) in a threaded mode; The surface of the outer tube (1) is provided with a through groove (14), the through groove (14) is rotationally connected with an adjusting rod (141), the adjusting rod (141) is connected with the groove wall of the through groove (14) through an adjusting spring (142), and the upper end of the screw rod (251) is provided with a straight groove (252) matched with the adjusting rod (141); the clamping unit comprises a clamping rod (261), a rectangular groove (26) is formed in the upper end wall of the clamping groove (241), the clamping rod (261) is connected in the rectangular groove (26) in a sliding and sealing mode, the clamping rod (261) is connected with the bottom of the rectangular groove (26) through a supporting spring (262), and a square groove (231) matched with the clamping rod (261) is formed in the surface of the connecting block (23); The clamping block (24) is provided with a cylindrical groove (27) communicated with the rectangular groove (26) at the lower end, the cylindrical groove (27) is rotationally connected with a rotating rod (271), one end, close to the bottom of the cylindrical groove (27), of the rotating rod (271) is connected with a threaded cylinder (272) in a threaded mode, and the threaded cylinder (272) is slidably connected in the cylindrical groove (27).
2. 2. The apparatus for synthesizing candesartan intermediate according to claim 1, wherein three rows of said tubular reactors are provided, at least two of said tubular reactors are provided in each row, two adjacent said tubular reactors are connected in series, and three of said tubular reactors are connected in series fixedly by a U-shaped tube (15).
3. 3. The apparatus for synthesizing candesartan intermediate according to claim 2 wherein said connecting grooves (216) have a cross-sectional shape of isosceles trapezoid.

Description

Synthetic candesartan apparatus for tam intermediates Technical Field The invention relates to the technical field of candesartan intermediate synthesis, in particular to equipment for synthesizing candesartan intermediates. Background Candesartan is an organic compound, belongs to an angiotensin II receptor antagonist, is used for treating human hypertension, has the characteristics of obvious curative effect, high safety and the like, however, the prodrug of candesartan is candesartan cilexetil, namely candesartan cilexetil needs to be rapidly hydrolyzed into an active metabolite candesartan in a patient to exert the drug effect, and 2-amino-3-nitrobenzoic acid methyl ester is a medical intermediate for synthesizing candesartan cilexetil; In the prior art, some technical schemes related to a preparation method of 2-amino-3-nitrobenzoic acid methyl ester also appear, for example, a Chinese patent with the publication number of CN111253271A discloses a method for preparing 2-amino-3-nitrobenzoic acid methyl ester, which comprises the following steps of pumping phthalimide solution and sodium hypochlorite solution into a micro-reactor for mixing, reacting with water to obtain methyl anthranilate, continuously separating to obtain crude product, pumping crude product of methyl anthranilate, acetic anhydride solution and fuming nitric acid into a micro-channel reactor for mixing and reacting to obtain methyl N-nitrobenzoate, continuously separating to obtain crude product, pumping the methyl N-nitrobenzoate solution, concentrated sulfuric acid and water into the micro-channel reactor for mixing and reacting to obtain the crude product of 2-amino-3-nitrobenzoate, and recrystallizing the crude product in methanol to obtain the product of 2-amino-3-nitrobenzoic acid methyl ester; However, when the tubular reactor is used, due to the influence of temperature fluctuation or uneven distribution of sodium hypochlorite, the phthalimide and the sodium hypochlorite are easy to generate side reaction to generate isomer byproducts such as aminobenzoic acid, metaaminobenzoic acid and the like, the solubility of the substances is low, precipitation is easy to form, the SK core piece clearance accumulation of the SK type static mixer which is precipitated in one of core components of the tubular reactor is caused (the SK type static mixer consists of a tube body and an inner SK core piece, the SK core piece is formed by welding spiral pieces which are twisted by 180 degrees left and right according to 90 degrees in a crossing way), the flow area is reduced, and because the SK core piece and the tube body are mainly welded and fixed (so as to prevent the SK core piece from being displaced due to material impact), the SK core piece cannot be detached and cleaned independently after blockage, the SK type static mixer is required to be replaced integrally, so that the purchase cost of equipment is obviously increased, in addition, the SK type static mixer is required to be stopped, the liquid in the side-by-side hollow tubular reactor is further increased, and the whole production efficiency is reduced; In view of the above, the present invention provides an apparatus for synthesizing candesartan intermediate, which solves the above technical problems. Disclosure of Invention In order to make up the defects of the prior art, the invention provides equipment for synthesizing the candesartan intermediate, and the equipment is provided with the SK core pieces which are detachably connected, so that a user can conveniently and independently detach the blocked SK core pieces, clean or replace the blocked SK core pieces, the expensive SK type static mixer is not required to be integrally replaced, the purchase cost of the equipment is greatly reduced, the complex disassembly and reassembly of the whole tubular reactor are not required, the shutdown time is obviously shortened, and the integral production efficiency of synthesizing the candesartan intermediate is further improved. The technical scheme adopted for solving the technical problems is that the equipment for synthesizing the candesartan intermediate comprises a micro-channel reactor, a tubular reactor and a continuous separator, wherein the tubular reactor also comprises an outer tube and a mixer arranged in the outer tube, the mixer comprises a tube body and an SK core piece, the SK core piece is formed by combining a plurality of spiral slices which are twisted by 180 degrees left and right, and the surface of the outer tube is provided with a liquid inlet and a liquid outlet; the pipe comprises a pipe body, a first flange, a second flange, a clamping unit and a clamping unit, wherein the first flange and the second flange are respectively arranged at two ends of the pipe body, bolt holes are formed in the surfaces of the first flange and the second flange, threaded holes opposite to the bolt holes are formed in the two ends of the outer pipe, the first flange is fixedly c