CN109503399B - Preparation method of Robenxib - Google Patents
Preparation method of Robenxib Download PDFInfo
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- CN109503399B CN109503399B CN201811646718.2A CN201811646718A CN109503399B CN 109503399 B CN109503399 B CN 109503399B CN 201811646718 A CN201811646718 A CN 201811646718A CN 109503399 B CN109503399 B CN 109503399B
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- C07C227/12—Formation of amino and carboxyl groups
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
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Abstract
The invention belongs to the technical field of production of non-steroidal anti-inflammatory drugs, and relates to a preparation method of Robencorxib, which comprises the following specific steps: under the protection of nitrogen, adding a solvent, 1- (2,3,5, 6-tetrafluorophenyl) indol-2-one and Lewis acid into a reaction bottle, controlling the temperature, dropwise adding ethyl bromide, continuously reacting for 3-6 hours after the dropwise adding is finished, cooling, slowly dropwise adding water, stirring and layering, washing an organic layer with water, drying, concentrating and crystallizing to obtain 5-ethyl-1- (2,3,5, 6-tetrafluorophenyl) indol-2-one; adding a solvent and an alkali into a reaction bottle, adding 5-ethyl-1- (2,3,5, 6-tetrafluorophenyl) indol-2-one, raising the temperature to 80-100 ℃, reacting for 5-10 h, adding hydrochloric acid to adjust the pH of a reaction solution to 3-4, filtering, washing an obtained solid product with water, and drying to obtain the Robenxib. The invention adopts a secondary Friedel-crafts alkylation method, thereby reducing the danger of reaction.
Description
Technical Field
The invention relates to a preparation method of Robencoxib, belonging to the technical field of production of non-steroidal anti-inflammatory drugs.
Background
Robucoxib (Robenacoxib), chemical name: 2- [2- (2,3,5, 6-tetrafluoroanilino) -5-ethylphenyl ] acetic acid, a non-steroidal anti-inflammatory drug used for pain relief, primarily for the treatment of arthritis, has fewer gastrointestinal adverse effects, has a lower risk of gastrointestinal ulceration and bleeding than other non-steroidal anti-inflammatory drugs (e.g. ibuprofen and naproxen), and is the only non-steroidal anti-inflammatory drug that has been demonstrated to have a lower incidence of such adverse effects.
Disclosure of Invention
The invention provides a preparation method of Robencoxib, which adopts a secondary Friedel-crafts alkylation method to reduce the risk of reaction.
The reaction formula for preparing the robucoxib is as follows:
wherein the compound (1) is 1- (2,3,5, 6-tetrafluorophenyl) indol-2-one, the compound (2) is 5-ethyl-1- (2,3,5, 6-tetrafluorophenyl) indol-2-one, and the compound (3) is robenib.
Specifically, an embodiment of the present invention comprises the steps of:
(1) synthesis of Compound 2:
under the protection of nitrogen, adding a solvent, a compound 1 and Lewis acid into a reaction bottle, controlling the temperature, dropwise adding bromoethane, continuously reacting for 3-6 hours, cooling, slowly dropwise adding water, stirring for layering, washing an organic layer with water, drying, concentrating and crystallizing to obtain a compound 2;
(2) synthesis of robucoxib:
adding a solvent and alkali into a reaction bottle, adding a compound 2, heating to 80-100 ℃, reacting for 5-10 h, adding hydrochloric acid to adjust the pH of a reaction solution to 3-4, filtering, washing an obtained solid product with water, and drying to obtain the Robenxib.
The synthesis of the compound 1 adopts the following method:
adding 230ml of dichlorobenzene and 54g of aluminum trichloride into a 500ml four-mouth reaction bottle under the protection of nitrogen, stirring at room temperature for 30min, adding 128g of 2-chloro-N- (2,3,5, 6-tetrafluorophenyl) -N-phenylacetamide, heating to 150 ℃, preserving heat, reacting for 6h, and finishing the reaction; cooling the reaction liquid to 50 ℃, pouring the reaction liquid into 600g of ice water for ice decomposition, and filtering the reaction liquid after the ice decomposition is finished; washing the obtained solid product with a large amount of water, then washing with a proper amount of n-hexane, and drying the solid product to obtain the compound 1.
Wherein in the step (1), the solvent is dichloromethane or trichloromethane; the Lewis acid is aluminum trichloride or ferric trichloride; the mole ratio of the Lewis acid to the compound 1 is (1-2): 1; the ratio of bromoethane to the compound 1 is (1.2-2): 1; the reaction temperature is 10-35 ℃, and the reaction time is 3-6 h;
in the step (2), the alkali is sodium hydroxide or potassium hydroxide, and the molar ratio of the alkali to the compound 2 is (2-3): 1; the solvent is water or a mixed solvent of water and methanol or water and ethanol, the reaction temperature is 80-100 ℃, and the reaction time is 5-10 h; the pH value of the reaction liquid crystal is 3-4.
Compared with the prior art, the invention has the advantages that:
compared with the synthetic method of the Robencoxib reported in the literature, the preparation method avoids the use of a catalyst dichloroethylaluminum with high risk in the process of Friedel-crafts cyclization, adopts a secondary Friedel-crafts alkylation method, and reduces the risk of reaction. The synthetic method has mature reaction types, low danger in industrialization and obvious practical value.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of Robinoxib prepared by the present invention.
FIG. 2 is a carbon spectrum of Robinoxib prepared according to the present invention.
FIG. 3 is a graph of mass spectrum (M-1) of Robinoxib prepared according to the present invention.
FIG. 4 is an IR spectrum of Robinoxib prepared according to the present invention.
Detailed Description
The present invention is further illustrated by the following specific examples.
Example 1:
(1) preparation of Compound 2
Adding 200ml of dichloromethane and 61g of aluminum trichloride into a 500ml four-mouth reaction bottle under the protection of nitrogen, then adding 128g of compound 1, then dropwise adding 59.5g of bromoethane at the temperature of 10-35 ℃, continuing to react for 3 hours after the dropwise adding is finished, then dropwise adding 200ml of water at the temperature of 10-35 ℃, stirring for half an hour after the dropwise adding is finished, standing for layering, washing a dichloromethane layer with 2 x 50ml of water, drying with anhydrous sodium sulfate, concentrating and crystallizing to obtain 125g of compound 2, wherein the yield is 88.8%.
(2) Preparation of Roben Coxib
Adding 600g of water and 42.7g of sodium hydroxide into a 1L four-mouth reaction bottle, then adding 100g of compound 2, heating to 100 ℃, and carrying out heat preservation reaction for 8 hours; then the temperature of the reaction solution is reduced to 60 ℃, hydrochloric acid is used for regulating the pH value to 3 for crystallization, the filtration is carried out, the obtained solid product is washed by water, the solid product is taken out and dried to obtain 96.3g of Robenxib, and the yield is 91%.
Example 2:
(1) preparation of Compound 2
Adding 200ml of trichloromethane and 130g of ferric trichloride into a 500ml four-mouth reaction bottle under the protection of nitrogen, adding 128g of the compound 1, then dropwise adding 60g of bromoethane at the temperature of 10-35 ℃, continuing to react for 6 hours after the dropwise adding is finished, then dropwise adding 200ml of water at the temperature of 10-35 ℃, stirring for half an hour after the dropwise adding is finished, standing for layering, washing a trichloromethane layer with 2 x 50ml of water, drying with anhydrous sodium sulfate, concentrating and crystallizing to obtain 128g of the compound 2, wherein the yield is 90.9%.
(2) Preparation of Roben Coxib
600g of water and 60g of potassium hydroxide are added into a 1L four-mouth reaction bottle, 100g of compound 2 is added, the temperature is raised to 80 ℃, the reaction is kept for 10 hours, then the reaction liquid is cooled to 60 ℃, the pH value is adjusted to 3 by hydrochloric acid, the filtration is carried out, the obtained solid product is washed by water, the solid product is taken out and dried to obtain 97.1g of Robenxib, and the yield is 91.7%.
Example 3:
(1) preparation of Compound 2
Adding 200ml of dichloromethane and 122g of aluminum trichloride into a 500ml four-mouth reaction bottle under the protection of nitrogen, then adding 128g of compound 1, then dropwise adding 60g of bromoethane at the temperature of 10-35 ℃, continuing to react for 3 hours after the dropwise adding is finished, then dropwise adding 200ml of water at the temperature of 10-35 ℃, stirring for half an hour after the dropwise adding is finished, standing for layering, washing a dichloromethane layer with 2-50 ml of water, drying with anhydrous sodium sulfate, concentrating and crystallizing to obtain 133g of compound 2, wherein the yield is 94.5%.
(2) Preparation of Roben Coxib
Adding 600g of water, 60g of methanol and 55g of potassium hydroxide into a 1L four-mouth reaction bottle, adding 100g of compound 2, heating to 90 ℃, keeping the temperature for reaction for 6h, evaporating to remove the methanol, then cooling the reaction solution to 50 ℃, adjusting the pH value to 4 with hydrochloric acid, filtering, washing the obtained solid product with water, taking out and drying to obtain 100.4g of Robenxib, wherein the yield is 94.87%.
Example 4:
(1) preparation of Compound 2
Adding 250ml of dichloromethane and 150g of ferric trichloride into a 500ml four-mouth reaction bottle under the protection of nitrogen, then adding 128g of compound 1, then dropwise adding 99.2g of bromoethane at the temperature of 10-35 ℃, continuing to react for 3 hours after the dropwise adding is finished, then dropwise adding 200ml of water at the temperature of 10-35 ℃, stirring for half an hour after the dropwise adding is finished, standing for layering, washing a dichloromethane layer with 2 x 50ml of water, drying with anhydrous sodium sulfate, concentrating and crystallizing to obtain 136.3g of compound 2, wherein the yield is 96.8%.
(2) Preparation of Roben Coxib
Adding 500g of water, 100g of ethanol and 28.4g of sodium hydroxide into a 1L four-mouth reaction bottle, adding 100g of compound 2, heating to 80 ℃, keeping the temperature, reacting for 5 hours, evaporating to remove the ethanol, cooling the reaction solution to 50 ℃, adjusting the pH value to 4 by using hydrochloric acid, filtering, washing the obtained solid product with water, taking out and drying to obtain 104.4g of Robenxib, wherein the yield is 98.7%.
Fig. 1 and fig. 2 show nuclear magnetic hydrogen spectrum and carbon spectrum of the robucoxib prepared by the invention. From fig. 1 it can be determined that: 10.2 to 9.0(br,1H, 16-position hydrogen atom), 7.11 to 7.09(m,2H,8, 10-position hydrogen atom), 6.87 to 6.85(m,1H, 5-position hydrogen atom), 6.77 to 6.62(m,2H,1, 7-position hydrogen atom), 3.82(s,2H, 12-position hydrogen atom), 2.68 to 2.60(m,2H, 14-position hydrogen atom), 1.28 to 1.23(m,3H, 15-position hydrogen atom); from fig. 2 it can be determined that: 179.90 ((carbon atom at position 13), 149.51 (carbon atom at position 2), 146.30 (carbon atom at position 3), 140.90 (carbon atom at position 9), 139.81 (carbon atom at position 10), 131.72 (carbon atom at position 8), 129.20 (carbon atom at position 6), 125.59 (carbon atom at position 4), 120.61 (carbon atom at position 7), 98.26 (carbon atom at position 1), 39.52 (carbon atom at position 12), 29.33 (carbon atom at position 14), and 16.75 (carbon atom at position 15).
The robucoxib structural formula is:
FIG. 3 is a mass spectrum of Robinoxib prepared according to the present invention. From fig. 3, the molecular weight of the compound can be determined: 327.
FIG. 4 is an IR spectrum of Robinoxib prepared according to the present invention. From fig. 4, the following can be resolved:
the analysis of the data can obtain that the substance prepared by the invention is the Robenxib.
Claims (8)
1. A method for preparing a rofecoxib, comprising the steps of:
(1) synthesis of 5-ethyl-1- (2,3,5, 6-tetrafluorophenyl) indol-2-one: under the protection of nitrogen, adding a solvent, 1- (2,3,5, 6-tetrafluorophenyl) indol-2-one and Lewis acid into a reaction bottle, controlling the temperature to be 10-35 ℃, dropwise adding bromoethane, continuing to react for 3-6 hours, cooling, slowly dropwise adding water, stirring and layering, washing and drying an organic layer, concentrating and crystallizing to obtain 5-ethyl-1- (2,3,5, 6-tetrafluorophenyl) indol-2-one; the Lewis acid in the step (1) is boron trifluoride, aluminum trichloride, ferric trichloride or antimony pentafluoride;
(2) synthesis of robucoxib: adding a solvent and an alkali into a reaction bottle, adding 5-ethyl-1- (2,3,5, 6-tetrafluorophenyl) indol-2-one, raising the temperature to 80-100 ℃, reacting for 5-10 h, adjusting the pH of a reaction solution to 3-4, filtering, washing an obtained solid product with water, and drying to obtain robenixib;
the reaction equations of the steps (1) and (2) are as follows:
the synthesis of the 1- (2,3,5, 6-tetrafluorophenyl) indol-2-ketone adopts the following method: adding dichlorobenzene and aluminum trichloride into a reaction bottle under the protection of nitrogen, stirring at room temperature for 30min, adding 2-chloro-N- (2,3,5, 6-tetrafluorophenyl) -N-phenylacetamide, heating to 150 ℃, preserving heat, reacting for 6h, and finishing the reaction; cooling the reaction liquid to 50 ℃, pouring the reaction liquid into ice water for carrying out the ice-out, and filtering the reaction liquid after the ice-out is finished; washing the obtained solid product with a large amount of water, then washing with n-hexane, and drying the solid product to obtain 1- (2,3,5, 6-tetrafluorophenyl) indol-2-one; the mass ratio of the 2-chloro-N- (2,3,5, 6-tetrafluorophenyl) -N-phenylacetamide to the aluminum trichloride is 1: 2.37.
2. The method for preparing robucoxib according to claim 1, wherein in step (1), the solvent is dichloromethane or trichloromethane.
3. The method for preparing robenixib according to claim 1, wherein the molar ratio of the Lewis acid to 1- (2,3,5, 6-tetrafluorophenyl) indol-2-one is (1-2): 1.
4. the method for preparing robenicoxib according to claim 1, wherein the molar ratio of bromoethane to 1- (2,3,5, 6-tetrafluorophenyl) indol-2-one in step (1) is (1.2-2): 1.
5. the method for preparing robucoxib according to claim 1, wherein the reaction temperature in step (1) is 10-35 ℃ and the reaction time is 3-6 h.
6. The method of claim 1, wherein the base in step (2) is sodium hydroxide or potassium hydroxide; the molar ratio of the base to the 5-ethyl-1- (2,3,5, 6-tetrafluorophenyl) indol-2-one is (2-3): 1.
7. the method for preparing robucoxib according to claim 1, wherein the solvent in step (2) is water or a mixed solvent of water and methanol or water and ethanol.
8. The method for preparing robucoxib according to claim 1, wherein the reaction temperature in step (2) is 80-100 ℃ and the reaction time is 5-10 h.
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| CN109694330B (en) * | 2017-10-24 | 2023-10-20 | 乳源瑶族自治县东阳光生物科技有限公司 | Preparation method of acid |
| CN110437090A (en) * | 2019-07-31 | 2019-11-12 | 江苏天和制药有限公司 | A kind of rofecoxib tripolymer and preparation method thereof |
| CN112679410A (en) * | 2019-10-17 | 2021-04-20 | 东莞市东阳光动物保健药品有限公司 | Preparation method of robucoxib intermediate |
| CN111807978B (en) * | 2020-07-29 | 2023-03-14 | 武汉川泰科技有限公司 | Preparation method of Robecoxib |
| EP4281183A1 (en) | 2022-03-23 | 2023-11-29 | Alivira Animal Health Limited | An improved process for purification of robenacoxib |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1140500C (en) * | 1997-08-28 | 2004-03-03 | 诺瓦提斯公司 | Certain 5-alkyl-2-arylaminophenylacetic acids and derivatives |
| CN102311355A (en) * | 2011-09-26 | 2012-01-11 | 扬州天和药业有限公司 | Preparation method of rofecoxib |
| CN106188190A (en) * | 2016-07-28 | 2016-12-07 | 威海迪素制药有限公司 | A kind of preparation method of the clean monohydrate of Tuo Gelie |
| CN107721901A (en) * | 2017-11-12 | 2018-02-23 | 刘磊 | A kind of preparation method of 2 [2 (2,3,5,6 phenyl tetrafluoride amido) phenyl] acetic acid |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2843504C (en) * | 2011-08-12 | 2020-08-25 | Ascendis Pharma A/S | Protein carrier-linked prodrugs |
| CN104803956A (en) * | 2015-03-06 | 2015-07-29 | 江苏天和制药有限公司 | Synthesis method of firocoxib |
-
2018
- 2018-12-29 CN CN201811646718.2A patent/CN109503399B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1140500C (en) * | 1997-08-28 | 2004-03-03 | 诺瓦提斯公司 | Certain 5-alkyl-2-arylaminophenylacetic acids and derivatives |
| CN102311355A (en) * | 2011-09-26 | 2012-01-11 | 扬州天和药业有限公司 | Preparation method of rofecoxib |
| CN106188190A (en) * | 2016-07-28 | 2016-12-07 | 威海迪素制药有限公司 | A kind of preparation method of the clean monohydrate of Tuo Gelie |
| CN107721901A (en) * | 2017-11-12 | 2018-02-23 | 刘磊 | A kind of preparation method of 2 [2 (2,3,5,6 phenyl tetrafluoride amido) phenyl] acetic acid |
Non-Patent Citations (3)
| Title |
|---|
| Activity Investigation of Imidazolium-Based Ionic Liquid as Catalyst for Friedel-Crafts Alkylation of Aromatic Compounds;Mingjian Cai，等;《Asian J. Chem》;20150110;第27卷(第2期);第649-653页 * |
| Preparation of 1,3,5-Tris(aminomethyl)-2,4,6-triethylbenzene from Two Versatile 1,3,5-Tri(halosubstituted) 2,4,6-Triethylbenzene Derivative;Karl J. Wallace，等;《Synthesis》;20050613;第2005卷(第12期);第2080页Scheme 1，第2082页左栏第2段 * |
| 罗本考昔合成过程中的副反应研究;刘磊，等;《广东化工》;20201231;第47卷(第15期);第99-101页 * |
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Denomination of invention: A preparation method of robbencoxib Effective date of registration: 20220129 Granted publication date: 20211224 Pledgee: Yangzhou Branch of Bank of Jiangsu Co.,Ltd. Pledgor: JIANGSU TIANHE PHARMACEUTICAL CO.,LTD. Registration number: Y2022980001366 |
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Date of cancellation: 20230328 Granted publication date: 20211224 Pledgee: Yangzhou Branch of Bank of Jiangsu Co.,Ltd. Pledgor: JIANGSU TIANHE PHARMACEUTICAL CO.,LTD. Registration number: Y2022980001366 |