CN101284852B - Piping production process of N-(2-hydroxyethyl)-beta-D-pyran glucosamine - Google Patents
Piping production process of N-(2-hydroxyethyl)-beta-D-pyran glucosamine Download PDFInfo
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- CN101284852B CN101284852B CN2008100621533A CN200810062153A CN101284852B CN 101284852 B CN101284852 B CN 101284852B CN 2008100621533 A CN2008100621533 A CN 2008100621533A CN 200810062153 A CN200810062153 A CN 200810062153A CN 101284852 B CN101284852 B CN 101284852B
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- hydroxyethyl
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- alcohol
- pyran glucosamine
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- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 title claims description 45
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 title claims description 45
- 229960002442 glucosamine Drugs 0.000 title claims description 45
- 238000004519 manufacturing process Methods 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 34
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- 239000002904 solvent Substances 0.000 claims abstract description 26
- 239000011259 mixed solution Substances 0.000 claims abstract description 24
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 21
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims abstract description 21
- 239000008103 glucose Substances 0.000 claims abstract description 17
- 239000012043 crude product Substances 0.000 claims abstract description 16
- 238000005576 amination reaction Methods 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- 239000007788 liquid Substances 0.000 claims description 27
- 229960001031 glucose Drugs 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000013078 crystal Substances 0.000 claims description 14
- KGWDUNBJIMUFAP-KVVVOXFISA-N Ethanolamine Oleate Chemical compound NCCO.CCCCCCCC\C=C/CCCCCCCC(O)=O KGWDUNBJIMUFAP-KVVVOXFISA-N 0.000 claims description 9
- 230000035484 reaction time Effects 0.000 claims description 9
- 238000002425 crystallisation Methods 0.000 claims description 7
- 230000008025 crystallization Effects 0.000 claims description 7
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 7
- SPFMQWBKVUQXJV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;hydrate Chemical compound O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O SPFMQWBKVUQXJV-BTVCFUMJSA-N 0.000 claims description 6
- 229960000673 dextrose monohydrate Drugs 0.000 claims description 6
- 238000001291 vacuum drying Methods 0.000 claims description 6
- 239000006188 syrup Substances 0.000 claims description 5
- 235000020357 syrup Nutrition 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 4
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 claims description 4
- 239000008121 dextrose Substances 0.000 claims description 4
- 229960004756 ethanol Drugs 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 2
- 239000012265 solid product Substances 0.000 claims description 2
- 238000010025 steaming Methods 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims 2
- 238000005265 energy consumption Methods 0.000 abstract description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 abstract 2
- 239000000243 solution Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- FRIYLLMQNCWJNL-RTRLPJTCSA-N OCCN[C@H]1C(O)O[C@@H]([C@H]([C@@H]1O)O)CO Chemical compound OCCN[C@H]1C(O)O[C@@H]([C@H]([C@@H]1O)O)CO FRIYLLMQNCWJNL-RTRLPJTCSA-N 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000005201 scrubbing Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
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- Saccharide Compounds (AREA)
Abstract
The invention discloses a method for realizing pipeline production of N-(2-ethoxyl)-Beta-D-glucopyranosylamine. The method is as follows: ethanolamine and glucose at the molar ratio of between 1:1 and 5:1 are used as a raw material which is mixed with solvent to obtain a mixed solution; the mixed solution is pumped into a pipeline reactor by a metering pump to carry out amination reaction, thereby obtaining a crude product solution containing N-(2-ethoxyl)-Beta-D-glucopyranosylamine under a pressure of between normal pressure and 2.0 MPa, at the temperature of between 40 and 80 DEG C for 10 to 30 mins. The method adopted to manufacture N-(2-ethoxyl)-Beta-D-glucopyranosylamine can obtain high rate of conversion at less energy consumption.
Description
Technical field
The present invention relates to a kind of chemical synthesis process, particularly a kind of method of utilizing pipeline reactor to prepare N-(2-hydroxyethyl)-β-D-pyran glucosamine.
Background technology
N-(2-hydroxyethyl)-β-D-pyran glucosamine is the important intermediate of antidiabetic medicine miglitol, and its structural formula is:
Chinese patent CN 1611485A in 2005 and Chinese patent CN 1962610A in 2007 have openly used the shortening single stage method directly to obtain the method for resemblance N-(2-hydroxyethyl)-glucosamine, but specifically do not mention the preparation process condition and the method for purification of N-(2-hydroxyethyl)-β-D-pyran glucosamine.
And patent CN 1063754C once disclosed a kind of method for preparing N-alkyl polyhydroxy alkylamine in moisture/hydroxylic solvent, had related to the method for this intermediate product of preparation in the tank reactor in this patent; But owing to adopt tank reactor, it is periodical operation, and the requirement of these reaction pair processing condition is harsh, and oversize in the comparatively high temps residence time as reactant, product color is darker, and by product increases, and influences quality product; If the reaction times is too short, then feed stock conversion is low.Therefore, this reaction technology haves much room for improvement.
In addition, above-mentioned patent does not all relate to the separating and purifying method of N-(2-hydroxyethyl)-β-D-pyran glucosamine.
Summary of the invention
The technical problem to be solved in the present invention provides the method for canalization production N-(the 2-hydroxyethyl)-β-D-pyran glucosamine of a kind of transformation efficiency height and less energy consumption.
In order to solve the problems of the technologies described above, the invention provides the method that a kind of canalization is produced N-(2-hydroxyethyl)-β-D-pyran glucosamine, be that 1: 1～5: 1 thanomin and glucose is raw material with mol ratio, raw material is mixed with solvent phase, must mixed solution; Mixed solution squeezed into volume pump carry out amination reaction in the pipeline reactor, must contain the crude product liquid of N-(2-hydroxyethyl)-β-D-pyran glucosamine, reaction pressure is that normal pressure～2.0Mpa, temperature of reaction are 40～80 ℃, reaction times 10～30mins.
Produce the improvement of the method for N-(2-hydroxyethyl)-β-D-pyran glucosamine as canalization of the present invention: the crude product liquid that will contain N-(2-hydroxyethyl)-β-D-pyran glucosamine carries out underpressure distillation, after steaming solvent, then add anhydrous alcohols and carry out crystallization, place after 36 hours, get crystal; With above-mentioned absolute alcohol class washing gained crystal 2～3 times, then 50 ℃ of following vacuum-dryings promptly get the white solid product again.
Produce the further improvements in methods of N-(2-hydroxyethyl)-β-D-pyran glucosamine as canalization of the present invention: the mass ratio of glucose and solvent is 1: 3～1: 6, and glucose is dextrose anhydrous, DEXTROSE MONOHYDRATE BP or high dextrose syrup etc.Solvent is the mixed solution of alcohol and water, and alcohol is 1: 1～5: 1 with the volume ratio of water; Alcohol particular methanol or ethanol, alcohol is 1: 1～2: 1 with the preferred volume ratio of water.
Produce the further improvements in methods of N-(2-hydroxyethyl)-β-D-pyran glucosamine as canalization of the present invention: in the amination reaction, the preferred molar ratio of thanomin and glucose is 1.05: 1～1.2: 1, glucose is 1: 3～1: 4 with the preferred mass ratio of solvent, 60～80 ℃ of preferable reaction temperature, preferred reaction pressure 1.0～2.0Mpa, preferred reaction time 10～20mins.
Produce the further improvements in methods of N-(2-hydroxyethyl)-β-D-pyran glucosamine as canalization of the present invention: the absolute alcohol kind solvent is at least a in anhydrous methanol and the dehydrated alcohol.Be that the absolute alcohol kind solvent is the mixture of anhydrous methanol, dehydrated alcohol or above-mentioned 2.
In the present invention, the crude product liquid that will contain N-(2-hydroxyethyl)-β-D-pyran glucosamine obtains red thick liquid after reducing pressure and removing solvent; Then red thick liquid is added the dissolving of absolute alcohol kind solvent, place crystallization in 36 hours under the room temperature, get crystal; Again with this crystal with above-mentioned absolute alcohol class repetitive scrubbing 2～3 times, 50 ℃ of following dryings obtain white solid.Detect with TLC point plate, product point is main point, can't see impure point substantially.
Canalization of the present invention is produced the method for N-(2-hydroxyethyl)-β-D-pyran glucosamine, has easy, practical, characteristics of high efficiency.Because the high mass-and heat-transfer efficient of pipeline reactor, thereby guarantee to be reflected at higher temperature of reaction and, can keep very high feed stock conversion than under the short residence time.Adopt N-(the 2-hydroxyethyl)-β-D-pyran glucosamine of the inventive method gained, have purity height, coloury advantage.
Compared with prior art, the present invention has following beneficial effect: the present invention adopts the canalization technology to make N-(2-hydroxyethyl)-β-D-pyran glucosamine, compare with traditional caldron process, simplified technology, realized the serialization of reaction process, and the amination reaction temperature is higher in the pipeline, and speed of response is fast.Products obtained therefrom purity after aftertreatment is higher, and color and luster is better, can be directly used in down the step hydrogenating reduction and prepare N-(2-hydroxyethyl)-glucosamine.
Synthetic route involved in the present invention is as follows:
Description of drawings
Below in conjunction with accompanying drawing the specific embodiment of the present invention is described in further detail.
Fig. 1 is the structural representation of the used pipeline reactor of the inventive method.
Embodiment
Embodiment 1, Fig. 1 have provided a kind of pipeline reactor, comprise head tank 1, volume pump 4, pipeline reactor 14 and condenser 11; The top of head tank 1 is respectively equipped with feed-pipe 15 and comb 17, is provided with stopping valve IV16 on feed-pipe 15, is provided with stopping valve V18 on comb 17.The outlet at bottom of head tank 1 links to each other with volume pump 4 by pipeline I3, volume pump 4 links to each other with the import of pipeline reactor 14 by pipeline II5, the outlet of pipeline reactor 14 links to each other with the import of condenser 11 by pipeline III9, and the outlet of condenser 11 links to each other with pipeline IV13.Be provided with stopping valve I2 on pipeline I3, be respectively equipped with tensimeter I6 and stopping valve II7 according to liquid flow direction on pipeline II5, pipeline reactor 14 is provided with thermometer 8, is provided with tensimeter II10 on pipeline III9, is provided with stopping valve III12 at pipeline IV13.
Thanomin, glucose and solvent after the metering be respectively in incoming stock jar 1 of feed-pipe 15 in proportion, and head tank 1 in uniform mixing, must mixed solution.Mixed solution enters through pipeline II5 under the effect of volume pump 4 after by pipeline I3 and carries out amination reaction in the pipeline reactor 14.The crude product liquid that contains N-(2-hydroxyethyl)-β-D-pyran glucosamine of reaction back gained enters condenser 11 by pipeline III9 and carries out condensation process; Condensed crude product liquid flows out from pipeline IV13.The stopping valve V18 that is arranged on the comb 17 plays safety valve.
Pipeline reactor 14 is that an internal diameter Φ is 1.4mm, wall thickness 0.8mm, and length is the drum type brake reactor of 30m; Reaction pressure in the pipeline reactor 14 is controlled jointly by stopping valve I2, stopping valve II7 and stopping valve III12, and volume pump 4 is used to regulate the flow velocity of mixed solution in pipeline reactor 14.Utilize tensimeter I6, can know from the pressure of volume pump 4 effusive mixed solutions in pipeline II5; Utilize tensimeter II10 can know from the pressure of pipeline reactor 14 effusive reaction product in pipeline III9.
The method that embodiment 2, a kind of canalization are produced N-(2-hydroxyethyl)-β-D-pyran glucosamine adopts embodiment 1 described pipeline reactor, carries out following steps successively:
1), preparation of raw material:
In head tank 1, add DEXTROSE MONOHYDRATE BP 33g (0.17mol), the solvent that each 50ml of first alcohol and water is formed; Shake up, DEXTROSE MONOHYDRATE BP is fully dissolved; And then add thanomin 13ml (0.20mol), shake up; Get mixed solution.
2), amination reaction:
With volume pump 4 above-mentioned mixed solution is squeezed in the pipeline reactor 14,60 ℃ of temperature of reaction, reaction pressure are normal pressure; The flow of control volume pump 4, making reactant (being mixed solution) is 140ml/h at the flow velocity of pipeline reactor, promptly the reaction times is about 20mins, follow the tracks of reaction with TLC, glucose point disappears, and finishes reaction, contains the crude product liquid of N-(2-hydroxyethyl)-β-D-pyran glucosamine.
3), aftertreatment:
(pressure obtains red thick liquid at 0.02～0.05MPa) time distilling off solvent first alcohol and water in decompression with the above-mentioned crude product liquid that contains N-(2-hydroxyethyl)-β-D-pyran glucosamine.In red thick liquid, add anhydrous methanol 10ml, place crystallization in 36 hours; The crystal of gained is cleaned twice repeatedly by anhydrous methanol once more, and filtration can obtain white crystal; 50 ℃ of following vacuum-dryings obtain white solid 32g.112～114 ℃ of its fusing points, yield 84.4% detects with TLC point plate, and product point is main point, can't see impure point substantially, detects through ESI-MS, and product really is target product N-(2-hydroxyethyl)-β-D-pyran glucosamine, and free from foreign meter substantially.
The method that embodiment 3, a kind of canalization are produced N-(2-hydroxyethyl)-β-D-pyran glucosamine adopts embodiment 1 described pipeline reactor, carries out following steps successively:
1), preparation of raw material:
In head tank 1, add dextrose anhydrous 30g (0.17mol), the solvent that methyl alcohol 60ml and water 50ml are formed; Shake up, dextrose anhydrous is fully dissolved; And then add thanomin 13ml (0.20mol), shake up; Get mixed solution.
2), amination reaction:
With volume pump 4 above-mentioned mixed solution is squeezed in the pipeline reactor 14,70 ℃ of temperature of reaction, reaction pressure are 1.0Mpa; The flow of control volume pump 4, making reactant (being mixed solution) is 180ml/h at the flow velocity of pipeline reactor, promptly the reaction times is about 15mins, follow the tracks of reaction with TLC, glucose point disappears, and finishes reaction, contains the crude product liquid of N-(2-hydroxyethyl)-β-D-pyran glucosamine.
3), aftertreatment:
With the above-mentioned crude product liquid that contains N-(2-hydroxyethyl)-β-D-pyran glucosamine distilling off solvent first alcohol and water under reduced pressure, obtain red thick liquid.In red thick liquid, add dehydrated alcohol 10ml, place crystallization in 36 hours; The crystal of gained is cleaned twice repeatedly by dehydrated alcohol once more, and filtration can obtain white crystal; 50 ℃ of following vacuum-dryings obtain white solid 33g.112～114 ℃ of its fusing points, yield 87.0% detects with TLC point plate, and product point is main point, can't see impure point substantially, detects through ESI-MS, and product really is target product N-(2-hydroxyethyl)-β-D-pyran glucosamine, and free from foreign meter substantially.
The method that embodiment 4, a kind of canalization are produced N-(2-hydroxyethyl)-β-D-pyran glucosamine adopts embodiment 1 described pipeline reactor, carries out following steps successively:
1), preparation of raw material:
In head tank 1, add DEXTROSE MONOHYDRATE BP 37g (0.19mol), the solvent that methyl alcohol 70ml and water 50ml are formed; Shake up, DEXTROSE MONOHYDRATE BP is fully dissolved; And then add thanomin 13ml (0.20mol), shake up; Get mixed solution.
2), amination reaction:
With volume pump 4 above-mentioned mixed solution is squeezed in the pipeline reactor 14,80 ℃ of temperature of reaction, reaction pressure are 2.0Mpa; The flow of control volume pump 4, making reactant (being mixed solution) is 277ml/h at the flow velocity of pipeline reactor, promptly the reaction times is about 10mins, follow the tracks of reaction with TLC, glucose point disappears, and finishes reaction, contains the crude product liquid of N-(2-hydroxyethyl)-β-D-pyran glucosamine.
3), aftertreatment:
With the above-mentioned crude product liquid that contains N-(2-hydroxyethyl)-β-D-pyran glucosamine distilling off solvent first alcohol and water under reduced pressure, obtain red thick liquid.In red thick liquid, add anhydrous methanol 10ml, place crystallization in 36 hours; The crystal of gained is cleaned twice repeatedly by anhydrous methanol once more, and filtration can obtain white crystal; 50 ℃ of following vacuum-dryings obtain white solid 35.7g.112～114 ℃ of its fusing points, yield 84.2% detects with TLC point plate, and product point is main point, can't see impure point substantially, detects through ESI-MS, and product really is target product N-(2-hydroxyethyl)-β-D-pyran glucosamine, and free from foreign meter substantially.
The method that embodiment 5, a kind of canalization are produced N-(2-hydroxyethyl)-β-D-pyran glucosamine adopts embodiment 1 described pipeline reactor, carries out following steps successively:
1), preparation of raw material:
In head tank 1, add high dextrose syrup (glucose quality mark 90%) 34g (0.17mol), the solvent that ethanol 120ml and water 30ml are formed; Shake up, high dextrose syrup is fully dissolved; And then add thanomin 55.25ml (0.85mol), shake up; Get mixed solution.
2), amination reaction:
With volume pump 4 above-mentioned mixed solution is squeezed in the pipeline reactor 14,40 ℃ of temperature of reaction, reaction pressure are 1.5Mpa; The flow of control volume pump 4, making reactant (being mixed solution) is 99ml/h at the flow velocity of pipeline reactor, promptly the reaction times is about 28mins, follow the tracks of reaction with TLC, glucose point disappears, and finishes reaction, contains the crude product liquid of N-(2-hydroxyethyl)-β-D-pyran glucosamine.
3), aftertreatment:
With the above-mentioned crude product liquid that contains N-(2-hydroxyethyl)-β-D-pyran glucosamine distilling off solvent second alcohol and water under reduced pressure, obtain red thick liquid.In red thick liquid, add dehydrated alcohol and each 40ml of anhydrous methanol, filtering and impurity removing (removing the insolubles in the syrup), filtrate is placed crystallization in 36 hours; The crystal of gained is cleaned twice repeatedly by the mixing liquid that dehydrated alcohol and anhydrous methanol are formed with 1: 1 volume ratio once more, and filtration can obtain white crystal; 50 ℃ of following vacuum-dryings obtain white solid 34g.112～114 ℃ of its fusing points, yield 85.8% detects with TLC point plate, and product point is main point, can't see impure point substantially, detects through ESI-MS, and product really is target product N-(2-hydroxyethyl)-β-D-pyran glucosamine, and free from foreign meter substantially.
At last, it is also to be noted that what more than enumerate only is several specific embodiments of the present invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be arranged.All distortion that those of ordinary skill in the art can directly derive or associate from content disclosed by the invention all should be thought protection scope of the present invention.
Claims (8)
1. a canalization is produced the method for N-(2-hydroxyethyl)-β-D-pyran glucosamine, it is characterized in that: with mol ratio is that 1: 1～5: 1 thanomin and glucose is raw material, described raw material is mixed with solvent phase, get mixed solution, described solvent is the mixed solvent of first alcohol and water or is the mixed solvent of second alcohol and water; Described mixed solution squeezed into volume pump carry out amination reaction in the pipeline reactor, must contain the crude product liquid of N-(2-hydroxyethyl)-β-D-pyran glucosamine, reaction pressure is that normal pressure～2.0Mpa, temperature of reaction are 40～80 ℃, reaction times 10～30mins.
2. canalization according to claim 1 is produced the method for N-(2-hydroxyethyl)-β-D-pyran glucosamine, it is characterized in that: the crude product liquid that will contain N-(2-hydroxyethyl)-β-D-pyran glucosamine carries out underpressure distillation, after steaming solvent, then add anhydrous alcohols and carry out crystallization, place after 36 hours, get crystal; With described anhydrous alcohols washing gained crystal 2～3 times, then 50 ℃ of following vacuum-dryings promptly get the white solid product again.
3. canalization according to claim 1 and 2 is produced the method for N-(2-hydroxyethyl)-β-D-pyran glucosamine, and it is characterized in that: the mass ratio of described glucose and solvent is 1: 3～1: 6.
4. canalization according to claim 3 is produced the method for N-(2-hydroxyethyl)-β-D-pyran glucosamine, and it is characterized in that: described glucose is dextrose anhydrous, DEXTROSE MONOHYDRATE BP or high dextrose syrup.
5. canalization according to claim 4 is produced the method for N-(2-hydroxyethyl)-β-D-pyran glucosamine, it is characterized in that: described solvent is the mixed solution of alcohol with water, and the volume ratio of described alcohol and water is 1: 1～5: 1.
6. canalization according to claim 5 is produced the method for N-(2-hydroxyethyl)-β-D-pyran glucosamine, and it is characterized in that: described alcohol is methyl alcohol or ethanol, and the volume ratio of described alcohol and water is 1: 1～2: 1.
7. canalization according to claim 6 is produced the method for N-(2-hydroxyethyl)-β-D-pyran glucosamine, it is characterized in that: in the described amination reaction, the mol ratio of thanomin and glucose is 1.05: 1～1.2: 1, the mass ratio of glucose and solvent is 1: 3～1: 4,60～80 ℃ of temperature of reaction, reaction pressure 1.0～2.0Mpa, reaction times 10～20mins.
8. canalization according to claim 2 is produced the method for N-(2-hydroxyethyl)-β-D-pyran glucosamine, it is characterized in that: described anhydrous alcohols is at least a in anhydrous methanol and the dehydrated alcohol.
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| CN102675160A (en) * | 2012-05-07 | 2012-09-19 | 黄冈永安药业有限公司 | Device and method for continuously producing sodium methyl taurate in pipeline mode |
| CN104151175B (en) * | 2014-08-18 | 2016-03-09 | 王秀梅 | A kind of miglitol impurity compound and its production and use |
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Non-Patent Citations (2)
| Title |
|---|
| Hodge, John E.等人.N-Glycosyl derivatives of secondary amines.《Journal of the American Chemical Society》.1952,第74卷 * |
| Mohammad, Ali等人.Relative stabilities of D-glucose amine derivatives.《Journal of the American Chemical Society》.1947,第69卷 * |
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