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Synthesis method of chlorthalidone medicine intermediate 2-(3-amino-4-chlorobenzoyl)benzoic acid

A technology of chlorobenzoyl and synthetic methods, which is applied in the field of organic synthesis, can solve the problems such as the need to improve the reaction yield and long reaction time, and achieve the effects of shortening the reaction time, increasing the reaction yield, and improving the reaction yield

Inactive Publication Date: 2016-08-31
CHENGDU DONG DIAN AI ER TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the reaction time is too long, generally more than 16 hours, and the reaction yield still needs to be improved. Therefore, it is necessary to propose a new synthetic method

Method used

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  • Synthesis method of chlorthalidone medicine intermediate 2-(3-amino-4-chlorobenzoyl)benzoic acid

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] A kind of synthetic method of chlorthalidone medicine intermediate 2-(3-amino-4-chlorobenzoyl)benzoic acid, carries out according to the following steps:

[0021] A, add 2-(3-nitro-4-chlorobenzoyl) benzoic acid (2) 0.23mol in reaction vessel, mass fraction is 35% sodium nitrate solution 300ml, mass fraction is 24% potassium carbonate solution 500ml, Raise the solution temperature to 60°C, add 1.3 L of 2-amino-5-chlorobenzoic acid solution with a mass fraction of 42%, 0.31 mol of cuprous chloride, 0.2 mol of potassium iodide, control the stirring speed at 160 rpm, and raise the solution temperature to 70 ℃, reflux for 3h;

[0022] B. Lower the solution temperature to 20°C, filter, wash the filter cake with a 52% sodium bisulfite solution in mass fraction, combine the washing liquid, raise the solution temperature to 50°C, add 300ml of ammonium chloride with a mass fraction of 37% Solution, fully stirred for 90min;

[0023] C. Reduce the solution temperature to 10°C, fi...

Embodiment 2

[0025] A kind of synthetic method of chlorthalidone medicine intermediate 2-(3-amino-4-chlorobenzoyl)benzoic acid, carries out according to the following steps:

[0026] A, add 2-(3-nitro-4-chlorobenzoyl) benzoic acid (2) 0.23mol in reaction vessel, mass fraction is 33% sodium nitrate solution 300ml, mass fraction is 24% potassium carbonate solution 500ml, Raise the solution temperature to 63°C, add 1.3 L of 2-amino-5-chlorobenzoic acid solution with a mass fraction of 42%, 0.31 mol of cuprous chloride, and 0.2 mol of potassium iodide, control the stirring speed at 170 rpm, and raise the solution temperature to 73 ℃, reflux for 3h;

[0027] B. Reduce the solution temperature to 23°C, filter, wash the filter cake with a 53% sodium bisulfite solution, combine the washing liquid, raise the solution temperature to 52°C, add 300ml of ammonium chloride with a mass fraction of 37% Solution, fully stirred for 110min;

[0028] C. Reduce the temperature of the solution to 13°C, filter...

Embodiment 3

[0030] A kind of synthetic method of chlorthalidone medicine intermediate 2-(3-amino-4-chlorobenzoyl)benzoic acid, carries out according to the following steps:

[0031] A, add 2-(3-nitro-4-chlorobenzoyl) benzoic acid (2) 0.23mol in reaction vessel, mass fraction is 37% sodium nitrate solution 300ml, mass fraction is 26% potassium carbonate solution 500ml, Raise the temperature of the solution to 65°C, add 1.3L of 2-amino-5-chlorobenzoic acid solution with a mass fraction of 45%, 0.31mol of cuprous chloride, and 0.2mol of potassium iodide, control the stirring speed at 190rpm, and raise the solution temperature to 76°C , reflux for 4h;

[0032] B, reduce solution temperature to 26 ℃, filter, filter cake is that 56% sodium bisulfite solution washes with mass fraction, merges washing liquid, raises solution temperature to 55 ℃, adds 300ml mass fraction and is 39% ammonium chloride solution, Fully stir for 130min;

[0033] C. Reduce the temperature of the solution to 15°C, filt...

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Abstract

The invention discloses a synthesis method of a chlorthalidone medicine intermediate 2-(3-amino-4-chlorobenzoyl)benzoic acid. The method comprises the following steps: reacting 2-(3-nitro-4-chlorobenzoyl)benzoic acid with cuprous chloride and potassium iodide, washing the obtained reaction product, carrying out suction pumping, and dehydrating the reaction product to obtain 2-(3-amino-4-chlorobenzoyl)benzoic acid. The whole reaction time is controlled to be 8h or shorter, and the reaction yield can reach 90% or above. The method provides a new synthesis route, and lays a good foundation for further increase of the reaction yield.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate, belonging to the field of organic synthesis, in particular to a synthesis method of 2-(3-amino-4-chlorobenzoyl)benzoic acid, a chlorthalidone pharmaceutical intermediate. Background technique [0002] Thiketone drugs are mainly used to treat congestive heart failure, liver cirrhosis ascites, nephrotic syndrome, acute and chronic nephritis edema, early chronic renal failure, sodium retention caused by adrenal corticosteroid and estrogen therapy. It can be used alone or in combination with other antihypertensive drugs, mainly for the treatment of essential hypertension. Oral absorption is incomplete, mainly combined with intracellular carbonic anhydrase, but little with plasma protein, and increased with plasma protein (mainly albumin) in severe anemia. It takes 2 hours to take effect after oral administration, the peak time is 2 hours, the duration of action is 24 to 72 hou...

Claims

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Application Information

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IPC IPC(8): C07C229/52C07C227/04
CPCC07C227/04C07C229/52
Inventor 储冬红
Owner CHENGDU DONG DIAN AI ER TECH
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