CN105037457A - Application of tolyltriazole in clindamycin phosphate synthesis - Google Patents
Application of tolyltriazole in clindamycin phosphate synthesis Download PDFInfo
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- CN105037457A CN105037457A CN201510445602.2A CN201510445602A CN105037457A CN 105037457 A CN105037457 A CN 105037457A CN 201510445602 A CN201510445602 A CN 201510445602A CN 105037457 A CN105037457 A CN 105037457A
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- clindamycin phosphate
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- triazole
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- JROIULXORPKSHX-ZDUSSCGKSA-N CCCC[C@]1(C)C[I](CNCCC)CC1 Chemical compound CCCC[C@]1(C)C[I](CNCCC)CC1 JROIULXORPKSHX-ZDUSSCGKSA-N 0.000 description 1
- XAZKFISIRYLAEE-ULUSZKPHSA-N C[C@H]1CC(C)CC1 Chemical compound C[C@H]1CC(C)CC1 XAZKFISIRYLAEE-ULUSZKPHSA-N 0.000 description 1
Abstract
The invention relates to an application of tolyltriazole in clindamycin phosphate synthesis. According to the application, pyridine and triethylamine are replaced by the tolyltriazole, so that the tolyltriazole, phosphorus oxychloride and a compound in a first formula can perform phosphate esterification reaction in solvent to obtain a solution of a compound in a second formula. A method for synthesizing the clindamycin phosphate is more efficient, low in cost, economical in energy and environmentally friendly due to the application of the tolyltriazole, and the obtained clindamycin phosphate is high in yield and purity.
Description
Technical field
The present invention relates to a kind of application of triazole, be specifically related to the application of a kind of triazole in synthesis Clindamycin Phosphate.
Background technology
Clindamycin Phosphate, chemical name is: (2S-is trans)-6-(1-methyl-4-propyl group-2-tetramethyleneimine carbonic acid amido)-1-sulfo--methyl-7-chloro-6,7,8-tri-deoxidation-L-Su Shi-α-D-noside-2-dihydrogen phosphoric acid ester, English name: ClindamycinPhosphate, molecular formula: C
18h
34clN
2o
8pS, molecular weight: 504.97, structural formula is:
In the process of synthesis Clindamycin Phosphate, phosphotidic reaction is committed step.This step of prior art is as follows:
But this reaction needed is (as about 0 DEG C) under cryogenic, phosphotidic reagent is generated by pyridine, triethylamine and phosphorus oxychloride, react with formula I and obtain phosphotidic product, that is: formula II compound, again gained phosphotidic product is hydrolyzed, then after purifying hydrolyzed solution (namely adsorb, wash, desorption, concentrated, crystallization and oven dry), obtain Clindamycin Phosphate finished product, there is following shortcoming in the method: 1, phosphotidic reaction requires to react at a lower temperature, and energy-output ratio is large; 2, the reaction conversion ratio of phosphotidic product hydrolysis is lower, and the purity of hydrolyzed solution is only about 90%, directly causes the total impurities of Clindamycin Phosphate higher, needs secondary crystal could meet the demand of high-end customer, makes production cost higher; 3, in phosphotidic reaction process, employ a large amount of pyridines, triethylamine, environmental pollution is serious.
Summary of the invention
In order to overcome the defect of prior art, the invention provides the application of a kind of triazole in synthesis Clindamycin Phosphate, organic bases pyridine and triethylamine is substituted with triazole in this application, make that the method for synthesis Clindamycin Phosphate is efficient, cost is low, energy-conserving and environment-protective, the productive rate of gained Clindamycin Phosphate is high, purity is high.
The application of a kind of triazole in synthesis Clindamycin Phosphate, wherein: replace pyridine and triethylamine with triazole, make triazole, phosphorus oxychloride and formula I carry out phosphotidic reaction acquisition formula II compound solution in a solvent, its chemical equation is as follows:
The application of triazole in synthesis Clindamycin Phosphate, wherein: the mass ratio of described formula I, triazole, phosphorus oxychloride is 1:0.2 ~ 0.4:1.2 ~ 1.3.
The application of triazole in synthesis Clindamycin Phosphate, wherein: described solvent is acetone.
The application of triazole in synthesis Clindamycin Phosphate, wherein: described in every 1g, formula I needs acetone 3 ~ 8ml, is preferably 3 ~ 5.
The application of triazole in synthesis Clindamycin Phosphate, wherein: the temperature of described phosphotidic reaction is 20 ~ 25 DEG C, and the reaction times is 3 ~ 5h.
The application of triazole in synthesis Clindamycin Phosphate, comprise the following steps: in described formula II compound solution, add water, be then hydrolyzed by soda acid adjusted to ph, obtain formula III compound solution, its chemical equation is as follows:
The application of triazole in synthesis Clindamycin Phosphate, wherein: during described hydrolysis, adjusted to ph is 9.5-10.5, is preferably pH10.0.
The application of triazole in synthesis Clindamycin Phosphate, wherein: described hydrolysis is temperature required is 0-25 DEG C, and required time is 6-8h.
The application of triazole in synthesis Clindamycin Phosphate, wherein: the concentration of described hydrolysis up-to-date style II compound is 75-85g/L, is preferably 80g/L.
In order to obtain Clindamycin Phosphate finished product, also to remove desolventizing by gained formula III compound solution according to a conventional method, obtaining hydrolyzed solution, resin absorption, washing, desorption is carried out to after hydrolyzed solution dilution, obtain stripping liquid, stripping liquid is concentrated, crystallization, obtains Clindamycin Phosphate finished product.
Compared with prior art, the present invention has following beneficial effect:
After substituting organic bases pyridine and triethylamine with triazole, the efficiency of phosphotidic reaction improves, and the reaction times is reduced to 3-5h by 8-10h; The temperature of reaction of phosphotidic reaction instead of low-temp reaction of the prior art by 20 ~ 25 DEG C, as 0 DEG C, thus the object reaching save energy, reduce costs; The productive rate of Clindamycin Phosphate finished product brings up to 90% by 70%, and in Clindamycin Phosphate finished product, the content of total impurities is reduced to 0.5% by 1%; Because the consumption of triazole is less than pyridine and triethylamine in phosphotidic reaction, controls the content of pyridine/triethylamine in phosphotidic reaction process waste water from source, thus significantly reduce the pressure of discharge of wastewater.
Embodiment
Below the specific embodiment of the present invention is described in detail, but is to be understood that protection scope of the present invention not by the restriction of embodiment.
Embodiment 1
(1) phosphotidic reaction: in 500ml reaction flask, add the formula I of 30g, 8.4g triazole, 180ml acetone successively, 22.2ml phosphorus oxychloride (density 1.645g/ml is dripped under controlling the condition of interior temperature 20 ~ 25 DEG C, 36.519g altogether), drip and finish, insulated and stirred 3h under the condition of interior temperature 20 ~ 25 DEG C, reaction terminates, and obtains formula II compound solution; The productive rate of this step compound of formula H is 97%, and purity is 98%;
(2) be hydrolyzed: add water by step 1 gained formula II compound solution, then use soda acid adjusted to ph, make formula II compound be 80g/L, pH10.0, the Water Under solution 8h of 20 DEG C in concentration, obtain formula III compound solution; The productive rate of this step compound of formula III is 98%, and purity is 96.7%;
(3) purifying: by formula III compound solution reduction vaporization removing acetone, obtain hydrolyzed solution, the purity of hydrolyzed solution compound of formula III is 96.7%, then being diluted to Clindamycin Phosphate concentration to hydrolyzed solution is according to a conventional method 2.5g/L, upper macroporous resin adsorbs, washing, then methyl alcohol desorption is used, obtain stripping liquid, distillation condensation place is concentrated under the condition of 50 DEG C without till water droplet drippage to stripping liquid, carry out crystallization with ethanol and obtain Clindamycin Phosphate finished product, from formula I to the productive rate 92% of Clindamycin Phosphate finished product, in gained finished product, total impurities content is 0.5%.
Embodiment 2
(1) phosphotidic reaction: in 500ml reaction flask, 23ml phosphorus oxychloride (density 1.645g/ml is dripped under adding the condition of temperature 20 ~ 25 DEG C in the formula I of 30g, 9g triazole, 150ml acetone, control successively, 37.835g altogether), drip and finish, insulated and stirred 4h under the condition of interior temperature 20 ~ 25 DEG C, reaction terminates, and obtains formula II compound solution; The productive rate of this step compound of formula H is 96.4%, and purity is 97.2%;
(2) be hydrolyzed: add water by step 1 gained formula II compound solution, then use soda acid adjusted to ph, make formula II compound be 75g/L, pH10.5, the Water Under solution 6h of 25 DEG C in concentration, obtain formula III compound solution; The productive rate of this step compound of formula III is 97.1%, purity 96.1%;
(3) purifying: by formula III compound solution reduction vaporization removing acetone, obtain hydrolyzed solution, the purity of hydrolyzed solution compound of formula III is 96.1%, then being diluted to Clindamycin Phosphate concentration to hydrolyzed solution is according to a conventional method 2.5g/L, upper macroporous resin adsorbs, washing, then methyl alcohol desorption is used, obtain stripping liquid, distillation condensation place is concentrated under the condition of 50 DEG C without till water droplet drippage to stripping liquid, carry out crystallization with ethanol and obtain Clindamycin Phosphate finished product, from formula I to the productive rate 90% of Clindamycin Phosphate finished product, in gained finished product, total impurities content is 0.6%.
Embodiment 1 and 2 gained Clindamycin Phosphate finished product is carried out nucleus magnetic hydrogen spectrum detection,
1hNMR DMX-500MHz nmr determination, solvent is D
2o, is inside designated as TSP, and gained hydrogen modal data is as follows:
1HNMR(D
2O)D/10-6:5.54(d,1H,J/Hz＝6)，4.50～4.53(m,1H)，3.81～3.85(m,1H)，4.31～4.35(m,1H)，3.90～3.93(m,1H)，4.41～4.44(m,1H)，4.55～4.65(m,1H)，1.44(d,3H,J/Hz＝6)，2.19(s,3H)，4.36～4.41(m,1H)，2.33～2.39(m,3H)，2.90～2.98(m,2H)，1.31～1.47(m,4H)，0.93(t,3H,J/Hz＝4)，2.95(s,3H)。
Confirm as Clindamycin Phosphate.
Embodiment 3 (comparative example of embodiment 1 and 2)
(1) phosphotidic reaction: in 500ml reaction flask, add the formula I of 30g, 18ml pyridine, 30ml triethylamine, 250ml acetone successively, 35ml phosphorus oxychloride (density 1.645g/ml is dripped under controlling the condition of interior temperature 0 DEG C, 57.575g altogether), drip and finish, insulated and stirred 8h under the condition of interior temperature 0 DEG C, reaction terminates, and obtains formula II compound solution; The productive rate of this step compound of formula H is 90.8%, and purity is 90.2%;
(2) be hydrolyzed: add water by step 1 gained formula II compound solution, then use soda acid adjusted to ph, be 80g/L, pH10.0, the Water Under solution 8h of 20 DEG C at formula II compound concentration, obtain formula III compound solution; The productive rate of this step compound of formula III is 75%, purity 87%;
(3) purifying: by formula III compound solution reduction vaporization removing acetone, obtain hydrolyzed solution, the purity of hydrolyzed solution compound of formula III is 87%, then being diluted to Clindamycin Phosphate concentration to hydrolyzed solution is according to a conventional method 2.5g/L, upper macroporous resin adsorbs, washing, then methyl alcohol desorption is used, obtain stripping liquid, distillation condensation place is concentrated under the condition of 50 DEG C without till water droplet drippage to stripping liquid, carry out crystallization with ethanol and obtain Clindamycin Phosphate finished product, from formula I to the productive rate 68% of Clindamycin Phosphate finished product, in gained finished product, total impurities content is 1.0%.
Embodiment 4
(1) chlorination reaction: by U 10149a 800 hundred million and chloroform 500L, Gu light 113.6kg, oxidation inhibitor AT-100.5kg, DMF120L at 50 ~ 80 DEG C, insulation reaction 25 hours, then be cooled to 0 DEG C;
(2) alcoholization reaction: add water 400L and 30% aqueous sodium hydroxide solution 200L in the solution of step (1) gained, be hydrolyzed at 20 DEG C, layering, extract organic layer, washing for twice with the trichloromethane of 136L, at 50 DEG C, concentrate out 500L chloroform, add dehydrated alcohol 80L again and carry out crystallization, obtain alcoholate;
(3) ketonize reaction: the insulation reaction 10h at 20 DEG C by the alcoholate 40kg of step (2) gained and acetone 160L, phosphorus oxychloride 14.5L; Obtain the acetone soln containing formula I 41.9kg;
(4) phosphotidic reaction: triazole 15kg is added the acetone soln of step (3) gained containing formula I 41.9kg, adding acetone 40L makes acetone cumulative volume be 200L, phosphorus oxychloride 30.6L (density 1.645g/ml is dripped under controlling the condition of interior warm 20-25 DEG C, 52.337kg altogether), insulated and stirred 4 hours;
(5) be hydrolyzed, purifying: add water in step (4) products therefrom, then soda acid adjusted to ph is used, be 80g/L at formula II compound concentration, pH10.0, the Water Under solution reaction 8h of 20 DEG C, reduction vaporization acetone again, obtain hydrolyzed solution, then being diluted to Clindamycin Phosphate concentration to hydrolyzed solution is according to a conventional method 2.5g/L, upper macroporous resin adsorbs, washing, then methyl alcohol desorption is used, obtain stripping liquid, carry out under the condition of 50 DEG C, being concentrated into distillation condensation place without till water droplet drippage to stripping liquid, carry out crystallization with ethanol and obtain Clindamycin Phosphate finished product.Productive rate 90% from lincomycin to Clindamycin Phosphate, in gained finished product, total impurities content is 0.5%.
Embodiment 5 (comparative example of embodiment 4)
(1)-(3) chlorination reaction of step, alcoholization reaction are identical with embodiment 4 with the condition that ketonize is reacted;
(4) phosphotidic reaction: pyridine 30L, triethylamine 35L are added the acetone soln of step 3 gained gained containing formula I 41.9kg, adding acetone 40L makes acetone cumulative volume be 200L, phosphorus oxychloride 40L is dripped, insulated and stirred 10 hours under controlling the condition of interior temperature 0 DEG C;
(5) be hydrolyzed, purifying: add water in step (4) products therefrom, then soda acid adjusted to ph is used, be 80g/L at formula II compound concentration, pH10.0, the condition hydrolysis reaction 8h of 20 DEG C, reduction vaporization acetone again, obtain hydrolyzed solution, then being diluted to Clindamycin Phosphate concentration to hydrolyzed solution is according to a conventional method 2.5g/L, upper macroporous resin adsorbs, washing, then methyl alcohol desorption is used, obtain stripping liquid, carry out under the condition of 50 DEG C, being concentrated into distillation condensation place without till water droplet drippage to stripping liquid, carry out crystallization with ethanol and obtain Clindamycin Phosphate finished product.Productive rate from lincomycin to Clindamycin Phosphate is 70%, and in gained finished product, total impurities content is 1.0%.
Be only specific embodiments of the invention above, but the present invention is not limited thereto, the changes that any person skilled in the art can think of all should fall into protection scope of the present invention.
Claims (9)
1. the application of triazole in synthesis Clindamycin Phosphate, it is characterized in that, replace pyridine and triethylamine with triazole, make triazole, phosphorus oxychloride and formula I carry out phosphotidic reaction acquisition formula II compound solution in a solvent, its chemical equation is as follows:
2. the application of triazole according to claim 1 in synthesis Clindamycin Phosphate, it is characterized in that, the mass ratio of described formula I, triazole, phosphorus oxychloride is 1:0.2 ~ 0.4:1.2 ~ 1.3.
3. the application of triazole according to claim 1 and 2 in synthesis Clindamycin Phosphate, it is characterized in that, described solvent is acetone.
4. the application of triazole according to claim 3 in synthesis Clindamycin Phosphate, it is characterized in that, described in every 1g, formula I needs acetone 3 ~ 8ml.
5. the application of triazole according to claim 4 in synthesis Clindamycin Phosphate, is characterized in that, the temperature of described phosphotidic reaction is 20 ~ 25 DEG C, and the time is 3 ~ 5h.
6. the application of triazole according to claim 5 in synthesis Clindamycin Phosphate, it is characterized in that, in described formula II compound solution, add water, be then hydrolyzed by soda acid adjusted to ph, obtain formula III compound solution, its chemical equation is as follows:
7. the application of triazole according to claim 4 in synthesis Clindamycin Phosphate, it is characterized in that, during described hydrolysis, adjusted to ph is 9.5-10.5, is preferably pH10.0.
8. the application of triazole according to claim 2 in synthesis Clindamycin Phosphate, it is characterized in that, described hydrolysis is temperature required is 0-25 DEG C, and required time is 6-8h.
9. the application of triazole according to claim 1 and 2 in synthesis Clindamycin Phosphate, it is characterized in that, the concentration of described hydrolysis up-to-date style II compound is 75-85g/L, is preferably 80g/L.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107652332A (en) * | 2017-10-11 | 2018-02-02 | 福安药业集团重庆博圣制药有限公司 | A kind of preparation method of clindamycin phosphate |
| CN107880083A (en) * | 2017-12-21 | 2018-04-06 | 广州白云山天心制药股份有限公司 | A kind of process for purification of clindamycin phosphate |
| CN108794550A (en) * | 2017-04-28 | 2018-11-13 | 浙江天台药业有限公司 | A method of preparing clindamycin phosphate |
| CN111825729A (en) * | 2020-07-14 | 2020-10-27 | 天方药业有限公司 | Purification method of clindamycin phosphate |
| USD922126S1 (en) | 2019-06-06 | 2021-06-15 | Sharkninja Operating Llc | User interface for a food preparation device |
| CN115141234A (en) * | 2022-07-14 | 2022-10-04 | 湖南恒生制药股份有限公司 | Synthesis process of clindamycin phosphate raw material medicine |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4895934A (en) * | 1988-08-22 | 1990-01-23 | E. I. Du Pont De Nemours And Company | Process for the preparation of clindamycin phosphate |
| US5182374A (en) * | 1990-03-21 | 1993-01-26 | American Cyanamid Company | Clindamycin phosphate synthesis |
| CN101298463A (en) * | 2007-09-19 | 2008-11-05 | 浙江天台药业有限公司 | Preparation of clindamycinum phosphoester |
| CN101704852A (en) * | 2009-11-17 | 2010-05-12 | 海南美兰史克制药有限公司 | Novel route for clindamycin phosphate compounds |
| CN101830946A (en) * | 2010-05-05 | 2010-09-15 | 南阳普康药业有限公司 | Method for synthesizing clindamycin phosphate |
| CN101891779A (en) * | 2010-06-17 | 2010-11-24 | 张家港市信谊化工有限公司 | Process for synthesizing clindamycin phosphate |
| CN103483399A (en) * | 2013-08-27 | 2014-01-01 | 河南天方药业股份有限公司 | Synthetic method of clindamycin phosphate |
-
2015
- 2015-07-27 CN CN201510445602.2A patent/CN105037457B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4895934A (en) * | 1988-08-22 | 1990-01-23 | E. I. Du Pont De Nemours And Company | Process for the preparation of clindamycin phosphate |
| US5182374A (en) * | 1990-03-21 | 1993-01-26 | American Cyanamid Company | Clindamycin phosphate synthesis |
| CN101298463A (en) * | 2007-09-19 | 2008-11-05 | 浙江天台药业有限公司 | Preparation of clindamycinum phosphoester |
| CN101704852A (en) * | 2009-11-17 | 2010-05-12 | 海南美兰史克制药有限公司 | Novel route for clindamycin phosphate compounds |
| CN101830946A (en) * | 2010-05-05 | 2010-09-15 | 南阳普康药业有限公司 | Method for synthesizing clindamycin phosphate |
| CN101891779A (en) * | 2010-06-17 | 2010-11-24 | 张家港市信谊化工有限公司 | Process for synthesizing clindamycin phosphate |
| CN103483399A (en) * | 2013-08-27 | 2014-01-01 | 河南天方药业股份有限公司 | Synthetic method of clindamycin phosphate |
Non-Patent Citations (1)
| Title |
|---|
| 蒋忠良等: "克林霉素磷酸酯的合成研究", 《同济大学学报(自然科学版)》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108794550A (en) * | 2017-04-28 | 2018-11-13 | 浙江天台药业有限公司 | A method of preparing clindamycin phosphate |
| CN107652332A (en) * | 2017-10-11 | 2018-02-02 | 福安药业集团重庆博圣制药有限公司 | A kind of preparation method of clindamycin phosphate |
| CN107880083A (en) * | 2017-12-21 | 2018-04-06 | 广州白云山天心制药股份有限公司 | A kind of process for purification of clindamycin phosphate |
| USD922126S1 (en) | 2019-06-06 | 2021-06-15 | Sharkninja Operating Llc | User interface for a food preparation device |
| CN111825729A (en) * | 2020-07-14 | 2020-10-27 | 天方药业有限公司 | Purification method of clindamycin phosphate |
| CN111825729B (en) * | 2020-07-14 | 2023-08-29 | 天方药业有限公司 | Purification method of clindamycin phosphate |
| CN115141234A (en) * | 2022-07-14 | 2022-10-04 | 湖南恒生制药股份有限公司 | Synthesis process of clindamycin phosphate raw material medicine |
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