CN106432099A - Method for fluorinating pyrimidine derivative by using micro-channel reactor - Google Patents
Method for fluorinating pyrimidine derivative by using micro-channel reactor Download PDFInfo
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- CN106432099A CN106432099A CN201510486694.9A CN201510486694A CN106432099A CN 106432099 A CN106432099 A CN 106432099A CN 201510486694 A CN201510486694 A CN 201510486694A CN 106432099 A CN106432099 A CN 106432099A
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- fluorine
- microchannel
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/553—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with halogen atoms or nitro radicals directly attached to ring carbon atoms, e.g. fluorouracil
Abstract
The invention discloses a method for directly fluorinating a pyrimidine derivative by using a micro-channel reactor. A uracil and/or cytosine and fluorine-containing acid and/or fluorine-containing alcohol mixture used as a raw material reacts with fluorine to prepare corresponding fluorouracil and/or fluorocytosine. The prepared fluorouracil and fluorocytosine have the advantages of high purity, low cost advantage, and safe and easily controlled fluorination process.
Description
Technical field
The present invention relates to a kind of method of pyrimidine derivatives fluorination, especially relate to one kind and carry out pyrimidine using micro passage reaction spread out
The method of biological fluorination.
Background technology
Pyrimidine derivatives are wide variety of in recent years new chemical drugs kinds, such as uracil, cytosine, thymus pyrimidine etc..For example
Typical uracil compounds 5-fluorouracil, its synthetic method has condensation and cyclization method and direct fluorination.Condensation and cyclization method is first
With fluoroformyl acetass enol form sodium salt and ureas or derivatives thereof cyclic condensation, then carry out post processing and obtain corresponding product, this
Method route length, yield are low, and product purification difficulty is big.Direct fluorination is the fluorine gas and pyrimidine derivates using noble gases dilution
Raw material direct reaction is obtained target product, and the method fluorine gas resource degree of danger is high, production process is wayward, production safety
Risk is big.
Micro passage reaction generally refers to the small-sized response system manufacturing through micro Process and precision processing technology, and it includes chemical industry
Blender needed for unit process, heat exchanger, reactor, controller etc., but its line size is much smaller than conventional tube reactor.
Different from the reactor of traditional open space formula, the fluid in micro passage reaction is in the space limited by, micro- logical
Under the collective effect of the structure in road, wellability and fluid phase content, in micro passage reaction, create biphase laminar flow, liquid (gas) post
The flow pattern that stream, drop (bubble) stream, annular flow etc. enrich.The micro passage reaction of for example big flux can be in higher flow velocity
Lower acquisition turbulent flow, in heterogeneous flow system, produces more horn of plenty with the introducing of immiscible fluid, micro passage reaction
Gas/liquid, liquid liquid, the multiphase flow pattern such as gas/liquid/liquid.And different flow patterns can bring different flow field situations, this is for anti-
The impact answering process is very significant.Simultaneously in micro passage reaction, due to exist boundary convection cell segmentation act on and
Microchannel for fluid rubbing action so that exist in micro passage reaction strong interior circulation and Secondary Flow flowing, this for
The mixing of strengthening reactant is also highly important.Therefore typically micro passage reaction is used for the violent reaction of heat release, reactant or product
The unstable reaction of thing, the exigent fast reaction of reactant ratio, hazardous chemical reaction, high-temperature high-voltage reaction and nanometer material
Expect and need product grain equally distributed solid reaction of formation.
Therefore, it is hopeful using micro passage reaction, the method carrying out pyrimidine derivatives fluorination for raw material with fluorine gas to be optimized.
Content of the invention
It is an object of the invention to using the characteristic of micro passage reaction, provide and a kind of directly fluorination can prepare the side of pyrimidine derivatives
Method, has the characteristics that high conversion, high selectivity, reaction are safely controllable.
The present invention provides following technical scheme：
A kind of fluorination process of pyrimidine derivatives, carries out fluorination reaction using micro passage reaction, comprises the following steps：
(1) raw material 2 is made to enter warm-up block, preheating temperature is -10～100 DEG C, described raw material 2 is uracil and/or born of the same parents are phonetic
Pyridine and the mixture of fluoric-containing acid and/or fluorine-containing alcohol；
(2) raw material 2 after making to preheat through step (1) and raw material 1 enter microchannel reaction module, and described raw material 1 is F2,
Raw material 2 and raw material 1 hybrid concurrency in the reaction module of described microchannel gives birth to fluorination reaction, described raw material 1 and raw material 2 mole
Proportioning is 0.8～2.0:1, raw material 2 flow be 1～100g/min, reaction temperature be -10～100 DEG C, reaction pressure be 0～
0.5MPa；
(3) step (2) microchannel is reacted and obtain corresponding fluorouracil after the product separating-purifying obtaining at module outlet
And/or fluorocytosin.
In the fluorination process that the present invention provides, the preheating temperature of step (1) raw material 2 is -10～100 DEG C, preferably -5～50 DEG C.
In the fluorination process that the present invention provides, it is mixed with fluoric-containing acid and/or fluorine-containing alcohol that described raw material 2 is uracil and/or cytosine
Compound it is possible to mixture include following several：Uracil and fluoric-containing acid；Uracil and fluorine-containing alcohol；Uracil, fluoric-containing acid
And fluorine-containing alcohol；Cytosine and fluoric-containing acid；Cytosine and fluorine-containing alcohol；Cytosine, fluoric-containing acid and fluorine-containing alcohol.In described mixture,
Preferably, uracil and/or cytosine are 3～15% with the mass ratio of fluoric-containing acid and/or fluorine-containing alcohol.Described fluoric-containing acid, preferably
Be selected from one of anhydrous hydrofluoric acid, trifluoroacetic acid and five fluorine propanoic acid, two or three.Described fluorine-containing alcohol, is preferably selected from
Trifluoroethanol and/or hexafluoroisopropanol.
In the fluorination process that the present invention provides, in described step (2), the mol ratio of described raw material 1 and raw material 2 is 0.8～
2.0:1.Preferably 1.0～1.2:1.
In the fluorination process that the present invention provides, in described step (2), raw material 2 flow is 1～100g/min.Preferably,
Raw material 2 flow is 10～50g/min.
The present invention provide fluorination process in, in described step (2), reaction temperature be -10～100 DEG C, reaction pressure be 0～
0.5MPa.Preferably, reaction temperature is -5～50 DEG C, and reaction pressure is 0～0.3MPa.
In the fluorination process that the present invention provides, in described step (2), the fluorine gas of use is preferably the fluorine being diluted by noble gases
Gas, that is, by F2With the gaseous mixture of noble gases composition, the volume content preferably 10～30mol% of fluorine gas.
In the fluorination process that the present invention provides, uracil and/or cytosine and F2Reaction generates corresponding fluorouracil and/or fluorine
For cytosine.Described fluorouracil, can be F atom be located at any one on uracil ring, two or more can be by F
The position that atom replaces.Preferably, described fluorouracil is 5-fluorouracil.Described fluorocytosin, can be that F is former
Son is located at any one on cytosine ring, two or more position that can be replaced by F atom.Preferably, described fluoro born of the same parents
Pyrimidine is 5-flurocytosine.
In the fluorination process that the present invention provides, described fluorination reaction is carried out in micro passage reaction, can be as desired by preheating
Module, reaction module, module is quenched and heat transfer module is attached.As an example, can connect into micro- logical shown in accompanying drawing 3
Road reactor assembly installation drawing.After micro passage reaction connects, it is possible to use conduction oil is conducted heat.
In the fluorination process that the present invention provides, as preferred mode, the mass tranfer coefficient of described micro passage reaction is 1～30Ka,
Exchange capability of heat is 1700KW/m2More than K.
In the fluorination process that the present invention provides, as preferred mode, described micro passage reaction is healthy and free from worry G2 microreactor, micro-
Hole array declines channel reactor, finned micro passage reaction, capillary microchannels reactor or multiply parallel type microreactor.
In the fluorination process that the present invention provides, the MCA in the reaction module of described micro passage reaction includes once-through type and leads to
Road structure and enhancing mixed type channel design.Preferably, described once-through type channel design is tubular structure, described enhancing mixing
Type channel design is T-type structure, spherical structure, spherical band baffle arrangement, drops structure or heart-shaped structure, and channel diameter
For 0.5mm～10mm.
The method that the present invention provides, due to needing to use F2It is preferred that the material of described microchannel reaction module is selected from carbonization
Silicon, Kazakhstan C alloy or manganese Nai Er alloy.
The method that the present invention provides compared to existing technology, has following advantage：The conversion ratio of raw material and selectivity height, purifying technique
Simplification, product purity height, low cost, process safety.
Brief description
Fig. 1 is the typical structure unit figure of micro passage reaction module used by the present invention；
Fig. 2 is for present invention institute in order to module map as a example Corning micro passage reaction；
Fig. 3 for present invention institute in order to micro channel reactor system installation drawing as a example Corning microchannel module, and in Fig. 3：1
For liquid phase pump (raw material 2 charging aperture), 2 be gas mass flow gauge (raw material 1 charging aperture), 3 be warm-up block, 4～9 be
Microchannel reaction module, 10 be module is quenched.
Specific embodiment
The present invention is further described with reference to specific embodiment, but do not limit the invention to these and be embodied as
Mode.One skilled in the art would recognize that present invention encompasses potentially included in Claims scope is all alternative
Scheme, improvement project and equivalents.
Embodiment 1
From 1 piece of corning straight channel module in accompanying drawing 2 (as premix warm-up block), corning " heart-shaped " microchannel
6 pieces of reaction module, 1 piece of corning straight channel module (as module is quenched) and 8 pieces of heat transfer module, according to accompanying drawing 3 institute
Show reaction process composition continuous stream microchannel response system.Reacting replacing heat medium adopts conduction oil.Forced according to micro passage reaction
Heat transfer theory, only arranges two points for measuring temperature in this reactor feed mouth and discharging opening.To microchannel response system and connection before reaction
Pipeline carries out eliminating water oil removal treatment respectively, carries out fluorine gas Passivation Treatment using 5mol% fluorine nitrogen mixed gas to system and connecting line,
Carry out 1.0MPa airtight test.By 1 liquid phase pump (as diaphragm metering pump) in accompanying drawing 3, connect to microchannel response system
Continuous stably addition uracil solution (i.e. the mixture of uracil and anhydrous hydrofluoric acid, uracil mass concentration 7%).By accompanying drawing 3
In 2 gas mass flow gauge, to microchannel response system continuous and quantitative add 20mol% fluorine nitrogen mixture gas.
Set 0 DEG C of heat exchange temperature, i.e. reaction temperature.Set reaction pressure 0.1MPa.Set uracil solution feed 20g/min,
20mol% fluorine nitrogen mixed gas feed 1.68L/min, and fluorine gas is 1.2 with the mol ratio of uracil:1.Reaction raw materials 2 uracil is molten
Liquid premixes through microchannel and enters " heart-shaped " microchannel reaction module 4 after warm-up block 3, and fluorine nitrogen mixed gas pass through gas mass flow
Gauge is directly entered " heart-shaped " microchannel reaction module 4, in the reaction module 4-9 of " heart-shaped " microchannel, fluorine nitrogen mixed gas
React with uracil.Crude reaction obtains liquid-phase product through being quenched after module 10 through gas-liquid separator separates, then through after system process,
5-fluorouracil product is obtained after drying.
To product liquid-phase chromatographic analysis, result shows, 5-fluorouracil purity reaches 98.6%, product yield 86.7%.
Embodiment 2
Using healthy and free from worry micro passage reaction similarly to Example 1, and according to same connected mode and control method.This enforcement
Example changes reaction condition.
Set -5 DEG C of heat exchange temperature, i.e. reaction temperature.Set reaction pressure 0.1MPa.Reaction raw materials 2 are uracil solution,
The i.e. mixture of uracil and trifluoroacetic acid, uracil mass concentration 7%, its charging rate is 100g/min.Raw material 1 is 30mol%
Fluorine nitrogen mixed gas, charging rate is 4.67L/min.Fluorine gas is 1 with the mol ratio of uracil:1.
Reaction raw materials 2 uracil solution premixes through microchannel and enters " heart-shaped " microchannel reaction module 4, fluorine after warm-up block 3
Nitrogen mixed gas are directly entered microchannel reaction module 4 by gas mass flow gauge, in " heart-shaped " microchannel reaction module 4-9
In, fluorine nitrogen mixed gas and uracil react.Crude reaction obtains liquid-phase product through being quenched after module 10 through gas-liquid separator separates,
Again through after system process, be dried after obtain 5-fluorouracil product.
To product liquid-phase chromatographic analysis, result shows, 5-fluorouracil purity reaches 98.1%, product yield 85.3%.
Embodiment 3
Using healthy and free from worry micro passage reaction similarly to Example 1, and according to same connected mode and control method.This enforcement
Example changes reaction condition.
Set 50 DEG C of heat exchange temperature, i.e. reaction temperature.Set reaction pressure 0.3MPa.Reaction raw materials 2 are uracil solution,
I.e. uracil and trifluoroacetic acid, the mixture of anhydrous hydrofluoric acid, uracil mass concentration 15%, wherein trifluoroacetic acid and anhydrous hydrogen
The quality proportioning of fluoric acid is 3:1, the charging rate of reaction raw materials 2 is 30g/min.Raw material 1 is 20mol% fluorine nitrogen mixed gas,
Charging rate is 5.4L/min.Fluorine gas is 1.2 with the mol ratio of uracil:1.
Reaction raw materials 2 uracil solution premixes through microchannel and enters " heart-shaped " microchannel reaction module 4, fluorine after warm-up block 3
Nitrogen mixed gas are directly entered microchannel reaction module 4 by gas mass flow gauge, in " heart-shaped " microchannel reaction module 4-9
In, fluorine nitrogen mixed gas and uracil react.Crude reaction obtains liquid-phase product through being quenched after module 10 through gas-liquid separator separates,
Again through after system process, be dried after obtain 5-fluorouracil product.
To product liquid-phase chromatographic analysis, 5-fluorouracil purity reaches 99.2%, product yield 78.4%.
Embodiment 4
Using healthy and free from worry micro passage reaction similarly to Example 1, and according to same connected mode and control method.This enforcement
Example changes reaction condition.
Set 0 DEG C of heat exchange temperature, i.e. reaction temperature.Set reaction pressure 0.15MPa.Reaction raw materials 2 are cytosine solution,
The i.e. mixture of cytosine and trifluoroacetic acid, uracil mass concentration 7%, its charging rate is 20g/min.Raw material 1 is 20mol%
Fluorine nitrogen mixed gas, charging rate is 1.69L/min.Fluorine gas is 1.2 with the mol ratio of cytosine:1.
Reaction raw materials 2 cytosine solution premixes through microchannel and enters " heart-shaped " microchannel reaction module 4, fluorine after warm-up block 3
Nitrogen mixed gas are directly entered microchannel reaction module 4 by gas mass flow gauge, in " heart-shaped " microchannel reaction module 4-9
In, fluorine nitrogen mixed gas and cytosine react.Crude reaction obtains liquid-phase product through being quenched after module 10 through gas-liquid separator separates,
Again through after system process, be dried after obtain 5-flurocytosine product.
To product liquid-phase chromatographic analysis, 5-flurocytosine purity reaches 98.6%, product yield 83.2%.
Embodiment 5
Using healthy and free from worry micro passage reaction similarly to Example 1, and according to same connected mode and control method.This enforcement
Example changes reaction condition.
Set 20 DEG C of heat exchange temperature, i.e. reaction temperature.Set reaction pressure 0.15MPa.Reaction raw materials 2 are cytosine solution,
The i.e. mixture of cytosine and hexafluoroisopropanol, uracil mass concentration 3%, its charging rate is 80g/min.Raw material 1 is 20mol%
Fluorine nitrogen mixed gas, charging rate is 2.90L/min.Fluorine gas is 1.2 with the mol ratio of cytosine:1.
Reaction raw materials 2 cytosine solution premixes through microchannel and enters " heart-shaped " microchannel reaction module 4, fluorine after warm-up block 3
Nitrogen mixed gas are directly entered microchannel reaction module 4 by gas mass flow gauge, in " heart-shaped " microchannel reaction module 4-9
In, fluorine nitrogen mixed gas and cytosine react.Crude reaction obtains liquid-phase product through being quenched after module 10 through gas-liquid separator separates,
Again through after system process, be dried after obtain 5-flurocytosine product.
To product liquid-phase chromatographic analysis, 5-flurocytosine purity reaches 99.3%, product yield 87.4%.
Embodiment 6
Using healthy and free from worry micro passage reaction similarly to Example 1, and according to same connected mode and control method.This enforcement
Example changes reaction condition.
Set -10 DEG C of heat exchange temperature, i.e. reaction temperature.Set reaction pressure 0.30MPa.Reaction raw materials 2 are cytosine solution,
The i.e. mixture of cytosine and trifluoroacetic acid, uracil mass concentration 3%, its charging rate is 50g/min.Raw material 1 is 10mol%
Fluorine nitrogen mixed gas, charging rate is 5.45L/min.Fluorine gas is 1.8 with the mol ratio of cytosine:1.
Reaction raw materials 2 cytosine solution premixes through microchannel and enters " heart-shaped " microchannel reaction module 4, fluorine after warm-up block 3
Nitrogen mixed gas are directly entered microchannel reaction module 4 by gas mass flow gauge, in " heart-shaped " microchannel reaction module 4-9
In, fluorine nitrogen mixed gas and cytosine react.Crude reaction obtains liquid-phase product through being quenched after module 10 through gas-liquid separator separates,
Again through after system process, be dried after obtain 5-flurocytosine product.
To product liquid-phase chromatographic analysis, 5-flurocytosine purity reaches 98.9%, product yield 78.3%.
Embodiment 7
Using healthy and free from worry micro passage reaction similarly to Example 1, and according to same connected mode and control method.This enforcement
Example changes reaction condition.
Set -10 DEG C of heat exchange temperature, i.e. reaction temperature.Set reaction pressure 0.3MPa.Reaction raw materials 2 are uracil solution,
The i.e. mixture of uracil and trifluoroacetic acid, uracil mass concentration 7%, its charging rate is 50g/min.Raw material 1 is 20mol%
Fluorine nitrogen mixed gas, charging rate is 4.2L/min.Fluorine gas is 1.2 with the mol ratio of uracil:1.
Reaction raw materials 2 uracil solution premixes through microchannel and enters " heart-shaped " microchannel reaction module 4, fluorine after warm-up block 3
Nitrogen mixed gas are directly entered microchannel reaction module 4 by gas mass flow gauge, in " heart-shaped " microchannel reaction module 4-9
In, fluorine nitrogen mixed gas and uracil react.Crude reaction obtains liquid-phase product through being quenched after module 10 through gas-liquid separator separates,
Again through after system process, be dried after obtain 5-fluorouracil product.
To product liquid-phase chromatographic analysis, 5-fluorouracil purity reaches 99.2%, product yield 89.4%.
Claims (9)
1. a kind of fluorination process of pyrimidine derivatives, it is characterised in that carrying out fluorination reaction using micro passage reaction, comprises the following steps：
(1) raw material 2 is made to enter warm-up block, preheating temperature is -10～100 DEG C, described raw material 2 is uracil and/or born of the same parents are phonetic
Pyridine and the mixture of fluoric-containing acid and/or fluorine-containing alcohol；
(2) raw material 2 after making to preheat through step (1) and raw material 1 enter microchannel reaction module, and described raw material 1 is F2,
Raw material 2 and raw material 1 hybrid concurrency in the reaction module of described microchannel gives birth to fluorination reaction, described raw material 1 and raw material 2 mole
Proportioning is 0.8～2.0:1, raw material 2 flow be 1～100g/min, reaction temperature be -10～100 DEG C, reaction pressure be 0～
0.5MPa；
(3) step (2) microchannel is reacted and obtain corresponding fluorouracil after the product separating-purifying obtaining at module outlet
And/or fluorocytosin.
2. according to the pyrimidine derivatives described in claim 1 fluorination process it is characterised in that in described step (1), preheating temperature is
- 5～50 DEG C.
3. according to the pyrimidine derivatives described in claim 1 fluorination process it is characterised in that in described raw material 2, fluoric-containing acid is selected from no
One of water Fluohydric acid., trifluoroacetic acid and five fluorine propanoic acid, two or three, fluorine-containing alcohol be selected from trifluoroethanol and/or hexafluoro isopropyl
Alcohol, uracil and/or cytosine are 3～15% with the mass ratio of fluoric-containing acid and/or fluorine-containing alcohol.
4. according to the pyrimidine derivatives described in claim 1 fluorination process it is characterised in that in described step (2), described raw material
1 is 1.0～1.2 with the mol ratio of raw material 2:1, raw material 2 flow is 10～50g/min, and reaction temperature is -5～50 DEG C,
Reaction pressure is 0～0.3MPa.
5. according to the pyrimidine derivatives described in claim 1 fluorination process it is characterised in that in described step (2), described by F2
In the gaseous mixture of noble gases composition, the volume content of fluorine gas is 10～30mol%.
6. according to the pyrimidine derivatives described in claim 1 fluorination process it is characterised in that described fluorouracil for 5- fluorine urinate phonetic
Pyridine, described fluorocytosin is 5-flurocytosine.
7. according to the pyrimidine derivatives described in claim 1 fluorination process it is characterised in that in described step (2), described microchannel
The material of reaction module is selected from carborundum, breathes out C alloy or manganese Nai Er alloy, and the mass tranfer coefficient of described micro passage reaction is 1～
30Ka, exchange capability of heat are 1700KW/m2More than K.
8. according to the pyrimidine derivatives described in claim 7 fluorination process it is characterised in that described micro passage reaction reaction module in
MCA include once-through type channel design and strengthen mixed type channel design, described once-through type channel design be tubular structure,
Described enhancing mixed type channel design is T-type structure, spherical structure, spherical band baffle arrangement, drops structure or heart-shaped structure,
And channel diameter is 0.5mm～10mm.
9. according to the pyrimidine derivatives described in claim 1 fluorination process it is characterised in that described micro passage reaction be healthy and free from worry G2 micro-
Reactor, microwell array decline channel reactor, finned micro passage reaction, capillary microchannels reactor or multiply cocurrent
Decline reactor.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107089952A (en) * | 2017-05-09 | 2017-08-25 | 宁夏蓝博思化学技术有限公司 | The method that 5 Flucytosines are prepared using micro passage reaction |
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| CN104326990A (en) * | 2014-10-16 | 2015-02-04 | 上虞华伦化工有限公司 | Method for fluoridating and synthesizing 5-flucytosine by cytosine |
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2015
- 2015-08-10 CN CN201510486694.9A patent/CN106432099A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104326990A (en) * | 2014-10-16 | 2015-02-04 | 上虞华伦化工有限公司 | Method for fluoridating and synthesizing 5-flucytosine by cytosine |
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| GERARD W.M.VISSER ET AL.: "Mechanism and Stereochemistry of the Fluorination of Uracil and Cytosine Using Fluorine and Acetyl Hypofluorite", 《J.ORG.CHEM.》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107089952A (en) * | 2017-05-09 | 2017-08-25 | 宁夏蓝博思化学技术有限公司 | The method that 5 Flucytosines are prepared using micro passage reaction |
| CN107089952B (en) * | 2017-05-09 | 2020-04-07 | 宁夏蓝博思化学技术有限公司 | Method for preparing 5-fluorocytosine by adopting microchannel reactor |
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Application publication date: 20170222 |