CN1830992A - Process for producing intermediate products with 9, 11 double bond of methylprednisolone series products - Google Patents
Process for producing intermediate products with 9, 11 double bond of methylprednisolone series products Download PDFInfo
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- CN1830992A CN1830992A CN 200510016283 CN200510016283A CN1830992A CN 1830992 A CN1830992 A CN 1830992A CN 200510016283 CN200510016283 CN 200510016283 CN 200510016283 A CN200510016283 A CN 200510016283A CN 1830992 A CN1830992 A CN 1830992A
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Abstract
The kind of the production process of the methylprednisolone series of product 9, 11-double bond intermediate is disclosed. With the use of the intermediate dehydrogenation substance for the raw material, the methyl sulfochlorides is conducted the sulphur esterify reaction; the reactive liquid is cool down when the reaction finish; the terminating water is dropwised adagio into the response liquid and the temperature is below the 30, so the sulfonylation substance cab be gained by diluting and filtrating when temperature levels off, the acetic acid, the sodium acetate and the sulfonylation substance acts; the methylprednisolone 9, 11-degreasing substance by diluting, filtrating and dryness when the reaction finish. The outcome can't be wrecked because of the unconspicuous advance of the temperature and the slow reaction between the water and the superfluous methane sulfonyl chloride during termination procedure, so the quality and the yield of the outcome are advanced.
Description
Technical field:
The present invention relates to methylprednisolone series product 9, the producing and manufacturing technique of the two key intermediates of 11---.
Background technology:
The producing and manufacturing technique of traditional methylprednisolone deestering material; with the intermediate dehydrogen substance is raw material; carry out sulfonylation with Methanesulfonyl chloride; low temperature slowly drips methylsulfonyl chloride down; the low temperature insulation reaction; reaction dilute, filter after finishing the wet product of methylprednisolone sulfonyl compound, with acetic acid, sodium-acetate and sulfonyl compound reaction, dilution after reaction finishes, filtration, the dry methylprednisolone deestering material that gets.Its shortcoming is: because the existence of excessive methylsulfonyl chloride, big calorimetric is emitted in dilution, and the sulfonylation structure is easily destroyed, causes principal product quality and yield not high.
Summary of the invention:
The present invention is directed to the problem that prior art exists, a kind of producing and manufacturing technique of methylprednisolone sulphonate is provided, is raw material with the intermediate dehydrogen substance, carries out the sulphur esterification with Methanesulfonyl chloride,
After reaction finished, with the reaction solution cooling, gradation slowly dripped termination water in reaction solution; temperature is treated to dilute, filter behind the temperature-stable below 30 ℃, gets the wet product of sulfonyl compound; with acetic acid, sodium-acetate and sulfonyl compound reaction, dilution after reaction finishes, filtration, the dry methylprednisolone deestering material that gets.Because the slow and water reaction of methylsulfonyl chloride that termination procedure is excessive, temperature increase is not obvious, can not damage product, and the quality of product and yield are improved.
In order to realize purpose of the present invention, the invention provides following technical scheme:
A kind of methylprednisolone series product 9, the producing and manufacturing technique of the two key intermediates of 11---is a raw material with the intermediate dehydrogen substance; carry out the sulphur esterification with Methanesulfonyl chloride, after reaction finishes, reaction solution is lowered the temperature; gradation slowly drips termination water in reaction solution; temperature is treated to dilute, filter behind the temperature-stable below 30 ℃, gets the wet product of sulfonyl compound; with acetic acid, sodium-acetate and sulfonyl compound reaction; dilution after reaction finishes, filtration, drying get methylprednisolone 9, the 11---deestering material.
Advantage of the present invention is slow and water reaction owing to the excessive methylsulfonyl chloride of termination procedure, and temperature increase is not obvious, can not damage product, and the quality of product and yield are improved.
Embodiment:
Embodiment 1: add the 30-40g pyridine with dehydrogen substance 10g; react in 5-10 ℃ with the 10-15g methylsulfonyl chloride; after reaction finishes; get the wet product of sulfonyl compound; react with 60g acetic acid, 25-30g sodium-acetate and sulfonyl compound; dilution after reaction finishes, filtration, the dry methylprednisolone deestering material 8.9g that gets, content 85%, yield are 89.0%.
Embodiment 2: add the 30-40g pyridine with dehydrogen substance 10g; react in 5-10 ℃ with the 10-15g methylsulfonyl chloride, after reaction finishes, reaction solution is lowered the temperature; in reaction solution, slowly drip and stop water 15ml; top temperature is controlled at below 20 ℃, and dilution, filtration get the wet product of sulfonyl compound; react with 60g acetic acid, 25-30g sodium-acetate and sulfonyl compound; dilution after reaction finishes, filtration, the dry methylprednisolone deestering material 9.32g that gets, content 88.6%, yield are 93.2%.
Embodiment 3: add the 30-40g pyridine with dehydrogen substance 10g; react in 5-10 ℃ with the 10-15g methylsulfonyl chloride, after reaction finishes, reaction solution is lowered the temperature; in reaction solution, slowly drip and stop water 25ml; top temperature is controlled at below 20 ℃, and dilution, filtration get the wet product of sulfonyl compound; react with 60g acetic acid, 25-30g sodium-acetate and sulfonyl compound; dilution after reaction finishes, filtration, the dry methylprednisolone deestering material 9.25kg that gets, content 88.4%, yield are 92.5%.
Embodiment 4: add the 30-40g pyridine with dehydrogen substance 10g; react in 5-10 ℃ with the 10-15g methylsulfonyl chloride, after reaction finishes, reaction solution is lowered the temperature; in reaction solution, slowly drip and stop water 25ml; top temperature is controlled at 30 ℃, and dilution, filtration get the wet product of sulfonyl compound; react with 60g acetic acid, 25-30g sodium-acetate and sulfonyl compound; dilution after reaction finishes, filtration, the dry methylprednisolone deestering material 9.35kg that gets, content 88.1%, yield are 93.5%.
Excellent beneficial effect of the present invention can experimental results show that by above.
Table 1: the producing and manufacturing technique of methylprednisolone deestering material of the present invention and existing effect are relatively
| Numbering | Dehydrogen substance is criticized charging capacity (g) | Production method | Methylprednisolone deestering material output (g) | Yield % | Improve yield % | Content % | Improve content % |
| 1 | 10 | Prior art | 8.9 | 89.0 | --- | 85.0 | --- |
| 2 | 10 | Add 15ml and stop water, top temperature is controlled at 20 ℃ | 9.32 | 93.2 | 4.72 | 88.6 | 4.24 |
| 3 | 10 | Add 25ml and stop water, top temperature is controlled at 20 ℃ | 9.25 | 92.5 | 3.93 | 88.4 | 4.0 |
| 4 | 10 | Add 25ml and stop water, top temperature is controlled at 30 ℃ | 9.35 | 93.5 | 5.06 | 88.1 | 3.65 |
Annotate: yield %=methylprednisolone deestering material output/dehydrogen substance is criticized charging capacity * 100%
Improve yield %=(methylprednisolone deestering material output-contrast methylprednisolone deestering material output) ÷ methylprednisolone
Above sulfonyl compound sample separates through thin-layer chromatography, is that 7: 3 the chloroform and the mixing solutions of acetone are made developping agent with volume ratio, adds the product impurity that stops water as can be seen and obviously is less than the product of not adding termination water.
As can be seen from the above table, add and stop more than the water 15ml, methylprednisolone deestering material yield and content all are significantly improved, and the raising degree of adding the yield that stops the above product of water 15ml and content is basic identical.
This shows, excellent beneficial effect of the present invention is: after reaction finishes, gradation slowly drips and stops more than the water 15ml in reaction solution, temperature is below 30 ℃, excessive methylsulfonyl chloride is reacted with water gradually, control the heat release speed that slows down, reduce that because temperature is too high product is produced the destructive degree, the quality of product and yield are improved.
Claims (1)
1. methylprednisolone series product 9; the producing and manufacturing technique of the two key intermediates of 11---; it is characterized in that: with the intermediate dehydrogen substance is raw material; carry out the sulphur esterification with Methanesulfonyl chloride; after reaction finishes; reaction solution is lowered the temperature; gradation slowly drips termination water in reaction solution; temperature is treated to dilute, filter behind the temperature-stable below 30 ℃, gets the wet product of sulfonyl compound; with acetic acid, sodium-acetate and sulfonyl compound reaction; dilution after reaction finishes, filtration, drying get methylprednisolone 9, the 11---deestering material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510016283 CN1830992A (en) | 2005-03-10 | 2005-03-10 | Process for producing intermediate products with 9, 11 double bond of methylprednisolone series products |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510016283 CN1830992A (en) | 2005-03-10 | 2005-03-10 | Process for producing intermediate products with 9, 11 double bond of methylprednisolone series products |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1830992A true CN1830992A (en) | 2006-09-13 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510016283 Pending CN1830992A (en) | 2005-03-10 | 2005-03-10 | Process for producing intermediate products with 9, 11 double bond of methylprednisolone series products |
Country Status (1)
| Country | Link |
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| CN (1) | CN1830992A (en) |
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2005
- 2005-03-10 CN CN 200510016283 patent/CN1830992A/en active Pending
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