CN112920030A - Method for preparing dapagliflozin intermediate by one-pot method - Google Patents
Method for preparing dapagliflozin intermediate by one-pot method Download PDFInfo
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Abstract
The invention discloses a method for preparing a dapagliflozin intermediate by a one-pot method, which comprises the following steps: reacting 5-bromo-2-chlorobenzoic acid with phenetole in the presence of an oxidant and a catalyst for a period of time, and purifying to obtain the gliflozin intermediate (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone. The method provided by the invention has high yield, simplifies the process steps of the traditional synthetic method, makes the process simpler, reduces the reaction cost and the impurity content, improves the purity and the yield, and better meets the industrial standard of benefit maximization.
Description
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a method for preparing a dapagliflozin intermediate by a one-pot method.
Background
Dapagliflozin (dapagliflozin) is a reversible and high-selectivity hypoglycemic drug which is developed by BaishiGuibao and Aslicon company in the United states and has a trade name of Farxiga, can be used as an important choice in the treatment of diabetes drugs, and is suitable for being used as an auxiliary diet and exercise for improving blood sugar control in type 2 diabetes adults. The HbA1c and fasting blood sugar of a type 2 diabetes patient can be obviously reduced, the incidence rate of adverse reactions is similar to that of a placebo, the risk of hypoglycemia is low, and the weight can be reduced, and the chemical structure of the composition is shown as follows:
in the prior art, the dapagliflozin is synthesized by mainly adopting an important intermediate, namely (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) ketone, as an initial raw material through reduction, coupling, reduction and deprotection, and the main synthetic route is as follows:
general synthesis scheme for (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone as shown below:
the method comprises the steps of using 5-bromo-2-chlorobenzoic acid as an initial raw material, carrying out acyl chlorination and Friedel-crafts acylation to obtain a compound (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone, wherein the preparation of an acyl chloride compound 5-bromo-2-chlorobenzoyl chloride is usually obtained by adding excessive oxalyl chloride or other thionyl chloride, phosphorus trichloride and other chlorination reactions, and then carrying out the Friedel-crafts reaction under the condition of excessive Lewis acid to obtain the compound (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone.
Although the above prior art discloses methods for the synthesis of (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone, which meet certain current needs, there are some disadvantages, especially the pollution and environmental problems, which need to be solved: for example, in the reaction process, because the dosage of the acyl chlorination reagent, Lewis acid represented by aluminum trichloride and the like is greatly excessive, the post-treatment is complicated, a large amount of acid gas and sewage are easily generated, and in addition, the problems of unsafe operation, potential safety hazard, low purity caused by easily generated impurities such as (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) ketone and the like exist.
Therefore, the development problem of the green preparation process of (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone still needs to be solved, which is one of the research hotspots and important solutions in the technical field.
Disclosure of Invention
The purpose of the invention is as follows: in order to solve the problems in the prior art, the invention provides a method for preparing a dapagliflozin intermediate by a one-pot method, which can solve the problems of complicated steps, environmental pollution and the like in the reaction process, can improve the reaction efficiency and the product purity, and is suitable for industrial production.
In order to achieve the purpose, the invention provides a method for preparing dapagliflozin intermediate (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) ketone by a one-pot method, which comprises the following reaction path:
concretely, 5-bromo-2-chlorobenzoic acid, red phosphorus, sodium bromide, anhydrous sodium carbonate powder and alpha-Fe2O3After stirring the molecular sieve and the oxidant in the reaction solvent uniformly, adding phenetole dropwise, preferably, adding phenetole dropwise at the speed of 0.15-0.2ml/min, more preferably, adding phenetole dropwise at the speed of 0.184ml/min on a laboratory scale, reacting for a period of time under constant temperature conditions, and obtaining the compound III, namely (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone after quenching, layering, concentrating, drying and recrystallizing.
Wherein the oxidant is any one or a mixture of more of tert-butyl hydroperoxide, potassium persulfate and hydrogen peroxide.
The molar ratio of the oxidant to the 5-bromo-2-chlorobenzoic acid is (1-2): 1, preferably 2: 1.
The reaction solvent is any one of N, N-dimethylformamide, 1, 4-dioxane, N-dimethylhexanamide, tetrahydrofuran and dichloroethane, and preferably 1, 4-dioxane.
Wherein, alpha-Fe2O3Is prepared by coprecipitation of iron (III) precursor and alkaline solution in a micro mixer, the 5-bromo-2-chlorobenzoic acid and the alpha-Fe2O3In a molar ratio of 1: (0.05-0.1), preferablyOptionally, 1: 0.08. specifically, iron (III) sulfate and ammonia were introduced into a micromixer, centrifuged, and the reddish brown precipitate was washed with water and ethanol, and then the obtained particles were dried under vacuum at 40 ℃ overnight, and finally, α -Fe was successfully prepared by calcining the reddish brown precipitate at 500 ℃ for 3 hours2O3。
Preferably, the molecular sieve is of type 3A, 4A or 5A, and the ratio of the mass of the molecular sieve added per ml of reaction solvent to the number of moles of the red phosphorus to the 5-bromo-2-chlorobenzoic acid is 1: (5-10), preferably 1: 10.
the molar ratio of the anhydrous sodium carbonate powder to the 5-bromo-2-chlorobenzoic acid is 1: (5-10), preferably 1: 10.
the molar ratio of the 5-bromo-2-chlorobenzoic acid to the phenetole is 1: (1-1.5), preferably 1: 1.5; the molar ratio of the 5-bromo-2-chlorobenzoic acid to the sodium bromide is 1: (0.03-0.05), preferably 1: 0.05.
preferably, the reaction temperature is 10 ℃ to 60 ℃ and the reaction time is 3 to 5 hours, more preferably, the reaction temperature is 40 ℃ and the reaction time is 4 hours.
The solvent for recrystallization is absolute ethyl alcohol.
The mechanism of the reaction process of the present invention is presumed as follows:
has the advantages that: compared with the prior art, the invention has the following advantages:
(1) the invention optimizes the process on the known path for synthesizing the (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) ketone, simplifies the operation and improves the product purity to a certain extent;
(2) the invention avoids the use of some dangerous chemicals, has relatively safe operation and reduces the pollution to the environment;
(3) the post-treatment method is simple in operation and reduces the process cost.
Drawings
FIG. 1 is a hydrogen spectrum of (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone;
FIG. 2 shows a carbon spectrum of (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone.
Detailed Description
The present invention will be described in further detail with reference to specific examples. The examples will help to understand the present invention given the detailed embodiments and the specific operation procedures, but the scope of the present invention is not limited to the examples described below.
Example 1
To the reaction tube were added 20mL of 1, 4-dioxane, 5-bromo-2-chlorobenzoic acid (2.35g), red phosphorus (123.89mg), sodium bromide (51.44mg), anhydrous sodium carbonate powder (105.99mg), α -Fe2O3(128.00mg), potassium persulfate (5.40g) and 4A type molecular sieve (2.00g), after stirring well at 40 ℃, after 0.184mL of phenetole (1.83g) was added dropwise per minute, after reaction for 4 hours at 40 ℃, quenching, layering, drying and concentration, recrystallization was carried out by absolute ethanol to obtain a white powdery solid, namely, (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone (3.04g, yield 90%, purity 99.5% by HPLC), whose hydrogen spectrum and carbon spectrum results are shown in FIG. 1 and FIG. 2.
1H NMR(400MHz,DMSO-d6)δ7.77–7.73(m,2H),7.70–7.67(m,2H),7.56(d,J=8.4Hz,1H),7.09–7.05(m,2H),4.13(q,J=7.0Hz,2H),1.35(t,J=7.0Hz,3H);
13C NMR(101MHz,DMSO-d6)δ191.65,163.95,140.97,134.49,132.69,132.19,131.53,129.32,128.49,120.81,115.27,64.29,14.90.HRMS(ESI)Calcd forC15H12BrClO2[M+H]+:338.9782;found:338.9780。
Example 2
To the reaction tube were added 20mL of 1, 4-dioxane, 5-bromo-2-chlorobenzoic acid (2.35g), red phosphorus (123.89mg), sodium bromide (51.44mg), anhydrous sodium carbonate powder (105.99mg), α -Fe2O3(128.00mg), potassium persulfate (5.40g) and A4 molecular sieve (2.00g) were added dropwise at 0.184mL/min after stirring well at 10 deg.CPhenetole (1.83g) was reacted at 10 ℃ for 5 hours, quenched, layered, dried, concentrated, and recrystallized from absolute ethanol to give a white powdery solid which was detected as (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone (2.63g, yield 72%, purity 99.0% by HPLC).
Example 3
To the reaction tube were added 20mL of 1, 4-dioxane, 5-bromo-2-chlorobenzoic acid (2.35g), red phosphorus (123.89mg), sodium bromide (51.44mg), anhydrous sodium carbonate powder (105.99mg), α -Fe2O3(128.00mg), potassium persulfate (5.40g) and A4 molecular sieve (2.00g) were stirred well at 60 ℃, phenetole (1.83g) was added dropwise at 0.184mL/min, and after reaction for 3 hours at 60 ℃, the mixture was quenched, layered, dried, concentrated, and recrystallized from absolute ethanol to give (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone (2.70g, yield 80%, yield 99.0% by HPLC) as a white powdery solid.
Example 4
To the reaction tube were added 20mL of N, N-dimethylformamide, 5-bromo-2-chlorobenzoic acid (2.35g), red phosphorus (61.94mg), sodium bromide (51.44mg), anhydrous sodium carbonate powder (105.99mg), α -Fe2O3(128.00mg), potassium persulfate (5.40g) and A4 molecular sieve (2.00g) were stirred well, phenetole (1.83g) was added dropwise at 0.184mL/min, after reaction at 40 ℃ for 4 hours, the mixture was quenched, layered, dried, concentrated, and recrystallized from absolute ethanol to give a white powdery solid which was detected as (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone (2.36g, yield 70%, purity 99.5% by HPLC).
Example 5
To the reaction tube were added 20mL of N, N-dimethylhexanamide, 5-bromo-2-chlorobenzoic acid (2.35g), red phosphorus (123.89mg), sodium bromide (51.44mg), anhydrous sodium carbonate powder (105.99mg), α -Fe2O3(128.00mg), potassium persulfate (5.40g) and A4 molecular sieve (2.00g) were stirred well at 40 ℃, phenetole (1.83g) was added dropwise at 0.184mL/min, after reaction for 4 hours at 40 ℃, quenched, layered, dried, concentrated, and recrystallized from absolute ethanol to give a white powdery solidIt was determined to be (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone (2.57g, 76% yield, 99.5% purity by HPLC).
Example 6
Tetrahydrofuran 20mL, 5-bromo-2-chlorobenzoic acid (2.35g), red phosphorus (123.89mg), sodium bromide (51.44mg), anhydrous sodium carbonate powder (105.99mg), α -Fe were added to the reaction tube2O3(128.00mg), potassium persulfate (2.70g) and A4 molecular sieve (2.00g) were stirred well at 40 ℃, phenetole (1.83g) was added dropwise at 0.184mL/min, after reaction for 4 hours at 40 ℃, quenching, layering, drying and concentration, and recrystallization from absolute ethanol gave a white powdery solid which was detected as (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone (2.30g, yield 68%, purity 99.5% by HPLC).
Example 7
To the reaction tube were added 20mL of dichloroethane, 5-bromo-2-chlorobenzoic acid (2.35g), red phosphorus (123.89mg), sodium bromide (30.86mg), anhydrous sodium carbonate powder (105.99mg), α -Fe2O3(128.00mg), potassium persulfate (5.40g) and A4 molecular sieve (2.00g) were stirred well at 40 ℃, phenetole (1.83g) was added dropwise at 0.184mL/min, after reaction for 4 hours at 40 ℃, quenched, layered, dried, concentrated, and recrystallized from absolute ethanol to give a white powdery solid which was detected as (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone (2.46g, yield 73%, purity 99.5% by HPLC).
Example 8
To the reaction tube were added 20mL of 1, 4-dioxane, 5-bromo-2-chlorobenzoic acid (2.35g), red phosphorus (123.89mg), sodium bromide (51.44mg), anhydrous sodium carbonate powder (105.99mg), α -Fe2O3(128.00mg), tert-butyl hydroperoxide (1.80g) and type 4A molecular sieve (2.00g) were stirred well at 40 ℃, phenetole (1.83g) was added dropwise at 0.184mL/min, and after reaction for 4 hours at 40 ℃, the mixture was quenched, layered, dried, concentrated, and recrystallized from absolute ethanol to give (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone (2.76g, yield 82%, purity 99.0% by HPLC).
Example 9
To the reaction tube were added 20mL of 1, 4-dioxane, 5-bromo-2-chlorobenzoic acid (2.35g), red phosphorus (123.89mg), sodium bromide (51.44mg), anhydrous sodium carbonate powder (105.99mg), α -Fe2O3(128.00mg), hydrogen peroxide (0.68g) and 4A type molecular sieve (2.00g) were stirred well at 40 ℃, after phenetole (1.83g) was added dropwise at 0.184mL/min, after reaction for 4 hours at 40 ℃, quenching, layering, drying and concentration, recrystallization was performed by absolute ethanol to obtain a white powdery solid, i.e., (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone (2.57g, yield 76%, purity 99.0% by HPLC).
The invention provides a thought and a method for preparing dapagliflozin intermediate by a one-pot method, and a plurality of methods and ways for realizing the technical scheme are provided, the above description is only a preferred embodiment of the invention, and it should be noted that for a person skilled in the art, a plurality of improvements and decorations can be made without departing from the principle of the invention, and the improvements and decorations should be regarded as the protection scope of the invention. All the components not specified in the present embodiment can be realized by the prior art.
Claims (10)
1. A method for preparing a dapagliflozin intermediate by a one-pot method, wherein the intermediate is (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) ketone, is characterized in that 5-bromo-2-chlorobenzoic acid, red phosphorus, sodium bromide, anhydrous sodium carbonate powder and alpha-Fe2O3Stirring the molecular sieve and the oxidant in a reaction solvent uniformly, adding phenetole at a certain dripping speed, reacting for a period of time at a constant temperature, quenching, layering, concentrating, drying, and recrystallizing to obtain a compound III, namely (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methanone.
2. The method according to claim 1, wherein the oxidant is any one or a mixture of t-butyl hydroperoxide, potassium persulfate and hydrogen peroxide.
3. The process according to claim 1 or 2, characterized in that the molar ratio of the oxidizing agent to 5-bromo-2-chlorobenzoic acid is (1-2): 1.
4. the method according to claim 1, wherein the reaction solvent is any one of N, N-dimethylformamide, 1, 4-dioxane, N-dimethylhexanamide, tetrahydrofuran and dichloroethane.
5. The method of claim 1, wherein α -Fe2O3Is prepared by coprecipitation of iron (III) precursor and alkaline solution in a micro mixer, the 5-bromo-2-chlorobenzoic acid and the alpha-Fe2O3In a molar ratio of 1: (0.05-0.1).
6. The process of claim 1, wherein the molecular sieve is of the 3A, 4A or 5A type and the mass of the molecular sieve added per ml of reaction solvent is from 0.1 to 0.2 g.
7. The process of claim 1, wherein the ratio of the moles of red phosphorus to the moles of 5-bromo-2-chlorobenzoic acid is from 1: (5-10).
8. The process according to claim 1, characterized in that the ratio of the number of moles of anhydrous sodium carbonate powder to the moles of 5-bromo-2-chlorobenzoic acid is 1: (5-10).
9. The process of claim 1, wherein the molar ratio of said 5-bromo-2-chlorobenzoic acid to said phenetole is 1: (1-1.5), wherein the molar ratio of the 5-bromo-2-chlorobenzoic acid to the sodium bromide is 1: (0.03-0.05).
10. The process according to claim 1, wherein the reaction temperature is 10 ℃ to 60 ℃ and the reaction time is 3 to 5 hours.
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113549042A (en) * | 2021-07-23 | 2021-10-26 | 安庆奇创药业有限公司 | Preparation method of dapagliflozin |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103570510A (en) * | 2012-07-19 | 2014-02-12 | 苏州中科天马肽工程中心有限公司 | One-pot synthesis method for 5-bromo-2-chloro-4'-ethoxy diphenylmethane |
CN104086379A (en) * | 2014-07-29 | 2014-10-08 | 安徽联创药物化学有限公司 | Method for synthesizing forxiga intermediate |
CN104478670A (en) * | 2014-11-17 | 2015-04-01 | 中国药科大学 | Preparation method of 5-bromine-2-chlorine-4'-ethyoxyl diphenylmethane |
CN107200683A (en) * | 2017-07-31 | 2017-09-26 | 青岛辰达生物科技有限公司 | A kind of preparation method for being used to treat type II diabetes Dapagliflozin intermediate |
CN107417515A (en) * | 2017-03-30 | 2017-12-01 | 上海常丰生物医药科技有限公司 | A kind of new method for synthesizing Dapagliflozin intermediate |
CN108250060A (en) * | 2018-01-26 | 2018-07-06 | 江苏尚莱特医药化工材料有限公司 | The synthetic method of the bromo- 2- chlorobenzoic acids of 5- |
CN110922305A (en) * | 2019-11-22 | 2020-03-27 | 南京正济医药研究有限公司 | Synthetic method of dapagliflozin intermediate 5-bromo-2-chloro-4' -ethoxy diphenylmethane |
CN111662166A (en) * | 2020-05-28 | 2020-09-15 | 吴赣药业(苏州)有限公司 | Preparation method of 5-bromo-2-chloro-4' -ethoxy diphenylmethane |
-
2021
- 2021-02-05 CN CN202110163161.2A patent/CN112920030A/en active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103570510A (en) * | 2012-07-19 | 2014-02-12 | 苏州中科天马肽工程中心有限公司 | One-pot synthesis method for 5-bromo-2-chloro-4'-ethoxy diphenylmethane |
CN104086379A (en) * | 2014-07-29 | 2014-10-08 | 安徽联创药物化学有限公司 | Method for synthesizing forxiga intermediate |
CN104478670A (en) * | 2014-11-17 | 2015-04-01 | 中国药科大学 | Preparation method of 5-bromine-2-chlorine-4'-ethyoxyl diphenylmethane |
CN107417515A (en) * | 2017-03-30 | 2017-12-01 | 上海常丰生物医药科技有限公司 | A kind of new method for synthesizing Dapagliflozin intermediate |
CN107200683A (en) * | 2017-07-31 | 2017-09-26 | 青岛辰达生物科技有限公司 | A kind of preparation method for being used to treat type II diabetes Dapagliflozin intermediate |
CN108250060A (en) * | 2018-01-26 | 2018-07-06 | 江苏尚莱特医药化工材料有限公司 | The synthetic method of the bromo- 2- chlorobenzoic acids of 5- |
CN110922305A (en) * | 2019-11-22 | 2020-03-27 | 南京正济医药研究有限公司 | Synthetic method of dapagliflozin intermediate 5-bromo-2-chloro-4' -ethoxy diphenylmethane |
CN111662166A (en) * | 2020-05-28 | 2020-09-15 | 吴赣药业(苏州)有限公司 | Preparation method of 5-bromo-2-chloro-4' -ethoxy diphenylmethane |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113549042A (en) * | 2021-07-23 | 2021-10-26 | 安庆奇创药业有限公司 | Preparation method of dapagliflozin |
CN113549042B (en) * | 2021-07-23 | 2022-09-27 | 安庆奇创药业有限公司 | Preparation method of dapagliflozin |
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