CN104447837A - Synthesis method for N-methoxymethyl-N-(trimethylsilyl methyl)benzylamine - Google Patents
Synthesis method for N-methoxymethyl-N-(trimethylsilyl methyl)benzylamine Download PDFInfo
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- CN104447837A CN104447837A CN201310416575.7A CN201310416575A CN104447837A CN 104447837 A CN104447837 A CN 104447837A CN 201310416575 A CN201310416575 A CN 201310416575A CN 104447837 A CN104447837 A CN 104447837A
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- benzylamine
- methoxymethyl
- trimethyl
- methylbenzylamine
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Abstract
The invention discloses a practical method for synthesis of N-methoxymethyl-N-(trimethylsilyl methyl)benzylamine. The reagent is widely used in synthesis of polysubstituted pyrrolidine compounds and medical intermediates.
Description
Technical field
The invention provides a kind of synthetic method of preparation N-methoxymethyl-N-(trimethyl silicane ylmethyl) benzylamine of practicality, this reagent is widely used in synthesizing polysubstituted pyrrolidine compound and medicine intermediate.
Background technology
In this year, polysubstituted pyrrolidine compound and medicine intermediate cause everybody and pay close attention to widely, come from the biological medicine activity that this compounds has.Pyrrolidines building block widely uses in a lot of new drug development field, and market demand is larger.The preparation method of current pyrrolidine compound there is no the method for synthesis polysubstituted pyrrole hydride compounds efficiently.N-methoxymethyl-N-(trimethyl silicane ylmethyl) benzylamine can form azomethine type Ye Li get in a mild condition, can carry out 1,3-cycloaddition with substituted olefine, provides various polysubstituted pyrrole alkane.
The structure of this reagent and with alkene carry out the mechanism of 1,3-cycloaddition following graphic shown in:
The domestic report not having the Patents technology of this reagent at present.
Summary of the invention
The present invention wants technical problem to be solved to be to provide a kind of practicality, the succinct method preparing high-purity N-methoxymethyl-N-(trimethyl silicane ylmethyl) benzylamine.Shown in our following equation of synthetic route:
Trimethyl chloromethyl base silane and benzylamine are having under solvent or condition of no solvent, and react under 100-200 degree celsius temperature, best temperature range is 110-130 degree Celsius; Reaction ratio is 1:1-3, and optimum proportioning is 2 ~ 3, obtains the trimethyl silicon based methylbenzylamine of intermediate.Next step could be used for after this product needed underpressure distillation purifying.
Trimethyl silicon based methylbenzylamine and formaldehyde react in methyl alcohol, and at-20 to 30 degrees Celsius, best temperature range is-10 to 5 degrees Celsius; Reaction ratio is 1:1-2, and best mol ratio is 1.3 ~ 1.7; Obtain crude product, obtain sterling through underpressure distillation.
Processing condition of the present invention can be carried out in wider scope, and the reaction conditions that the present invention enumerates such as solvent/temperature/reaction ratio/substrate selection etc. is not restrictive, and only correspond to preferred conclusion of the present invention.
Below will illustrate method of the present invention by specific examples.
Embodiment
Below by following instance, the present invention is further detailed.The synthesis technique that example of the present invention is stated is only for illustration of the present invention, instead of limitation of the present invention.In operational path situation of the present invention to present invention process carry out simple modifications all belong to application claims protection content.
Example one:
Take trimethyl chloromethyl base silane (245.4g, 2mol) in there-necked flask, emptying logical nitrogen protection, heat temperature raising.Start when temperature rises to 85 DEG C slowly to drip BnNH
2(556.4g, 5.2mol), system slowly heats up, and control temperature of reaction at 120 DEG C, about 3-4h is by BnNH
2dropwise, continue maintenance system in 120 DEG C of reaction about 12h, after complete reaction, stop heating.After system is cooled to room temperature, crosses and filter solid substance, filter cake sherwood oil (150ml × 2) embathes to be filtered dry and remains to product-free, collects filter cake (benzylamine hydrochloride); Washing lotion filtrate merges (about 1000ml), with about 4L moisture washing three to four times; Organic phase Anhydrous potassium carbonate and anhydrous sodium sulphate combination drying, organic phase underpressure distillation removes 100 DEG C-200 DEG C, the process of concentrated solution vapor rectification process, collects the trimethyl silicon based methylbenzylamine of main distillate fraction and obtains 331.2g, yield 85.6%, GC content 98.4%.
Example two:
Take trimethyl chloromethyl base silane (245.4g, 2mol) in there-necked flask, emptying logical nitrogen protection, heat temperature raising.Start when temperature rises to 85 DEG C slowly to drip BnNH
2(428g, 4mol), system slowly heats up, and control temperature of reaction at 100 DEG C, about 3-4h is by BnNH
2dropwise, continue maintenance system in 200 DEG C of reaction about 5h, after complete reaction, stop heating.After system is cooled to room temperature, crosses and filter solid substance, filter cake sherwood oil (150ml × 2) embathes to be filtered dry and remains to product-free, collects filter cake (benzylamine hydrochloride); Washing lotion filtrate merges (about 1000ml), with about 4L moisture washing three to four times; Organic phase Anhydrous potassium carbonate and anhydrous sodium sulphate combination drying, organic phase underpressure distillation removes 100 DEG C-200 DEG C, the process of concentrated solution vapor rectification process, collects the trimethyl silicon based methylbenzylamine of main distillate fraction and obtains 320g, yield 82%, GC content 98.2%.
Example three:
Take formalin (37%) (198.7g; 2.52mol) in 250ml there-necked flask; emptying logical nitrogen protection; cryosel bath is cooled to 0 DEG C; again by trimethyl silicon based methylbenzylamine (331.2g; 1.72mol) drop in there-necked flask; control temperature 0 DEG C, throws stirring reaction 1h after finishing, then add Anhydrous potassium carbonate (187.4g in batches at-5 DEG C; 1.39mol); finish and add methyl alcohol (229.2g, 7.15mol) again, stop cooling; be warming up to room temperature, stirring is spent the night.React complete, filtrate stratification, get its upper strata underpressure distillation and remove a small amount of methyl alcohol, concentrated that product N-methoxymethyl-N-(trimethyl silicane ylmethyl) benzylamine is about crude product 364.3g.77-80 degree cut is collected in underpressure distillation under 0.5 mmhg pressure can obtain colourless liquid 300g sterling, yield 73%.
Example four:
Take formalin (37%) (198.7g; 2.52mol) in 250ml there-necked flask, emptying logical nitrogen protection, at 20 DEG C again by trimethyl silicon based methylbenzylamine (331.2g; 1.72mol) drop in there-necked flask; control temperature 0 DEG C, throws stirring reaction 1h after finishing, then add Anhydrous potassium carbonate (187.4g in batches at 20 DEG C; 1.39mol); finish and add methyl alcohol (229.2g, 7.15mol) again, room temperature for overnight.React complete, filtrate stratification, get its upper strata underpressure distillation and remove a small amount of methyl alcohol, concentrated that product N-methoxymethyl-N-(trimethyl silicane ylmethyl) benzylamine is about crude product 364g.77-80 degree cut is collected in underpressure distillation under 0.5 mmhg pressure can obtain colourless liquid 180g sterling, yield 44%.
Claims (6)
1. prepare an efficiently succinct method for trimethyl silicon based methylbenzylamine, with trimethyl chloromethyl base silane and benzylamine for the direct single step reaction of raw material obtains.
2. the method for claim 1, is characterized in that: reaction ratio is 1:1-3, and optimum proportioning is 2 ~ 3.
3. the method for claim 1, is characterized in that: temperature of reaction can at 100-200 degree Celsius, and best temperature range is 110-130 degree Celsius.
4. a trimethyl silicon based methylbenzylamine and formaldehyde react the method preparing N-methoxymethyl-N-(trimethyl silicane ylmethyl) benzylamine in methyl alcohol.
5. method as claimed in claim 4, is characterized in that: the reaction ratio of two reaction substrates can be 1 ~ 2, and better mol ratio is 1.3 ~ 1.7.
6. method as claimed in claim 4, is characterized in that: temperature of reaction can at-20 to 30 degrees Celsius, and best temperature range is-10 to 5 degrees Celsius.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310416575.7A CN104447837A (en) | 2013-09-13 | 2013-09-13 | Synthesis method for N-methoxymethyl-N-(trimethylsilyl methyl)benzylamine |
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| CN201310416575.7A CN104447837A (en) | 2013-09-13 | 2013-09-13 | Synthesis method for N-methoxymethyl-N-(trimethylsilyl methyl)benzylamine |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107473976A (en) * | 2016-06-08 | 2017-12-15 | 中国科学院大连化学物理研究所 | A kind of preparation method of N methoxyl methyls aminated compounds |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006019886A2 (en) * | 2004-07-14 | 2006-02-23 | Bristol-Myers Squibb Company | Pyrrolo(oxo)isoquinolines as 5ht ligands |
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- 2013-09-13 CN CN201310416575.7A patent/CN104447837A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006019886A2 (en) * | 2004-07-14 | 2006-02-23 | Bristol-Myers Squibb Company | Pyrrolo(oxo)isoquinolines as 5ht ligands |
Non-Patent Citations (1)
| Title |
|---|
| 谢洪磊等，: "吡咯烷-3-羧酸甲酯的合成", 《化学通报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107473976A (en) * | 2016-06-08 | 2017-12-15 | 中国科学院大连化学物理研究所 | A kind of preparation method of N methoxyl methyls aminated compounds |
| CN107473976B (en) * | 2016-06-08 | 2019-07-12 | 中国科学院大连化学物理研究所 | A kind of preparation method of N- methoxyl methyl aminated compounds |
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