CN102675190A - Synthesis method of 3-(dimethylamino)methyne-N-mesylpiperidyl-4-one - Google Patents
Synthesis method of 3-(dimethylamino)methyne-N-mesylpiperidyl-4-one Download PDFInfo
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- CN102675190A CN102675190A CN2012101619518A CN201210161951A CN102675190A CN 102675190 A CN102675190 A CN 102675190A CN 2012101619518 A CN2012101619518 A CN 2012101619518A CN 201210161951 A CN201210161951 A CN 201210161951A CN 102675190 A CN102675190 A CN 102675190A
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- methyne
- dimethylamino
- methylsulfonyl
- piperidin
- methylsulfonyl piperidin
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Abstract
The invention discloses a synthesis method of 3-(dimethylamino)methyne-N-mesylpiperidyl-4-one, which comprises the following steps: carrying out mesyl protection on the accessible raw material 4-piperidone hydrochloride hydrate, and carrying out dimethyl aldolization on the 4-piperidone hydrochloride hydrate and N,N-dimethyl formamide to obtain the 3-(dimethylamino)methyne-N-mesylpiperidyl-4-one. The method has the advantage of high yield, is easy to operate and purify, and is suitable for industrial production.
Description
Technical field
The present invention relates to the synthesis technique of a kind of 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-, belong to medicine, chemical technology field.
Background technology
A kind of 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-is a kind of brown solid, is the important intermediate raw materials of many medicine intermediates.
Summary of the invention
The present invention is a raw material with the 4-piperidone hydrochloride hydrate that is easy to get; Methylsulfonyl protection on the nitrogen earlier; At N, with N, the reaction of dinethylformamide dimethylacetal obtains 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-in the dinethylformamide again.This method yield is high, good operation, and good purifying is fit to suitability for industrialized production.
The compound method of 3-according to the invention (dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-is that 4-piperidone hydrochloride hydrate is dissolved in the mixed solvent of chloroform and water, adds salt of wormwood and does alkali; Cooling drips methylsulfonyl chloride down; Add ambient temperature overnight, through simply extraction, evaporate to dryness promptly gets white solid N-methylsulfonyl piperidin-4-one-after the Diluted Acid Washing drying; N-methylsulfonyl piperidin-4-one-is dissolved in N, in the dinethylformamide 100
oC and N after the reaction of dinethylformamide dimethylacetal, add water filtration and promptly get brown solid 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-.
The compound method the first step of above-mentioned 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-is synthesized N-methylsulfonyl piperidin-4-one-; It is characterized in that: the solvent of going up the basic methylsulfonyl of protection on the nitrogen is the mixed solvent of water and chloroform, and raw material 4-piperidone hydrochloride is the 4-piperidone hydrochloride hydrate of the band crystal water that is easy to get on the market, has reduced raw materials cost; Aftertreatment is simple; Extraction, weak acid scrubbing promptly gets white solid N-methylsulfonyl piperidin-4-one-behind the dry evaporate to dryness.
Synthetic 3-(dimethylamino) methyne of second step of the compound method-N-methylsulfonyl piperidin-4-one-of above-mentioned 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-; It is characterized in that: reaction finishes; Behind the cool to room temperature; After adding entry under stirring, solid is separated out filtration and has just been obtained brown solid product 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-.
Above-mentioned with 4-piperidone hydrochloride hydrate, methylsulfonyl chloride, N, dinethylformamide dimethylacetals etc. are following for synthetic 3-(dimethylamino) methyne of raw material-N-methylsulfonyl piperidin-4-one-chemical reaction and reaction formula:
(1) reaction equation of 4-piperidone hydrochloride hydrate and methylsulfonyl chloride is:
(2) N-methylsulfonyl piperidin-4-one-is dissolved in N, in the dinethylformamide 100
oC and N, dinethylformamide dimethylacetal reaction equation is:
Embodiment
Embodiment
Salt of wormwood (900 grams; 6.51 mole) join and dissolved 4-piperidone hydrochloride hydrate (250 grams; 1.63 in mole) the chloroform (800 milliliters) and water (800 milliliters) mixing solutions, mechanical stirring obtains a suspension liquid, ice-water bath is cooled to zero degree; In a hour time, dripped methylsulfonyl chloride (377 milliliters, 4.5 moles).Add the back ambient temperature overnight, add methylene dichloride (1.5 liters) and saturated sodium bicarbonate solution (1.5 liters) again, separatory, water are used methylene dichloride (1.5 liters) extraction again.Merge organic phase, after the potassium hydrogen sulfate solution with 1% (1 liter) washing, concentrating under reduced pressure obtains white solid N-methylsulfonyl piperidin-4-one-(250 gram) behind the dried over mgso after-filtration.
N-methylsulfonyl piperidin-4-one-(227 grams, 1.28 moles) is dissolved in N, and dinethylformamide (1 liter) adds N, dinethylformamide dimethylacetal (208.3 milliliters, 1.575 moles).This solution is heated to 100
oC, reaction is spent the night.Behind the cool to room temperature, add 2 liters water after, solid is separated out, and filters to obtain brown solid, after the washing of small amount of cold ETHYLE ACETATE, vacuum-drying obtains brown solid 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-(180 restrain).
Claims (4)
1. the compound method of 3-according to the invention (dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-is that 4-piperidone hydrochloride hydrate is dissolved in the mixed solvent of chloroform and water, adds salt of wormwood and does alkali; Cooling drips methylsulfonyl chloride down; Add ambient temperature overnight, through simply extraction, evaporate to dryness promptly gets white solid N-methylsulfonyl piperidin-4-one-after the Diluted Acid Washing drying; N-methylsulfonyl piperidin-4-one-is dissolved in N, in the dinethylformamide 100
oC and N after the reaction of dinethylformamide dimethylacetal is spent the night, add water filtration and promptly get brown solid 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-.
2. the compound method of 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-as claimed in claim, it is characterized in that: described initial feed is meant that 4-piperidone hydrochloride hydrate is a raw material.
3. the compound method the first step of above-mentioned 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-is synthesized N-methylsulfonyl piperidin-4-one-; It is characterized in that: the solvent of going up the basic methylsulfonyl of protection on the nitrogen is the mixed solvent of water and chloroform, and raw material 4-piperidone hydrochloride is the 4-piperidone hydrochloride hydrate of the band crystal water that is easy to get on the market, has reduced raw materials cost; Aftertreatment is simple; Extraction, weak acid scrubbing promptly gets white solid N-methylsulfonyl piperidin-4-one-behind the dry evaporate to dryness.
4. synthetic 3-(dimethylamino) methyne of second step of the compound method-N-methylsulfonyl piperidin-4-one-of above-mentioned 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-; It is characterized in that: reaction finishes; Behind the cool to room temperature; After adding entry under stirring, solid is separated out filtration and has just been obtained brown solid product 3-(dimethylamino) methyne-N-methylsulfonyl piperidin-4-one-.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101619518A CN102675190A (en) | 2012-05-23 | 2012-05-23 | Synthesis method of 3-(dimethylamino)methyne-N-mesylpiperidyl-4-one |
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| CN2012101619518A CN102675190A (en) | 2012-05-23 | 2012-05-23 | Synthesis method of 3-(dimethylamino)methyne-N-mesylpiperidyl-4-one |
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| CN2012101619518A Pending CN102675190A (en) | 2012-05-23 | 2012-05-23 | Synthesis method of 3-(dimethylamino)methyne-N-mesylpiperidyl-4-one |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030073672A1 (en) * | 2001-09-05 | 2003-04-17 | Breitenbucher J. Guy | Method for treating allergies using substituted pyrazoles |
| CN1911913A (en) * | 2001-07-26 | 2007-02-14 | 先灵公司 | New neuropeptide YY5 receptor antagonists |
| CN102007126A (en) * | 2008-02-22 | 2011-04-06 | Irm责任有限公司 | Compounds and compositions as modulators of gpr119 activity |
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2012
- 2012-05-23 CN CN2012101619518A patent/CN102675190A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1911913A (en) * | 2001-07-26 | 2007-02-14 | 先灵公司 | New neuropeptide YY5 receptor antagonists |
| US20030073672A1 (en) * | 2001-09-05 | 2003-04-17 | Breitenbucher J. Guy | Method for treating allergies using substituted pyrazoles |
| CN102007126A (en) * | 2008-02-22 | 2011-04-06 | Irm责任有限公司 | Compounds and compositions as modulators of gpr119 activity |
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Application publication date: 20120919 |