CN104356186B - A kind of preparation method of 3 ', 5 ' dioxies (4 pairs of methyl benzoyls) β L thymus pyrimidines - Google Patents
A kind of preparation method of 3 ', 5 ' dioxies (4 pairs of methyl benzoyls) β L thymus pyrimidines Download PDFInfo
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- CN104356186B CN104356186B CN201410574599.XA CN201410574599A CN104356186B CN 104356186 B CN104356186 B CN 104356186B CN 201410574599 A CN201410574599 A CN 201410574599A CN 104356186 B CN104356186 B CN 104356186B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
Abstract
Of the invention a kind of 3 '; the preparation method of 5 ' dioxies (4 pairs of methyl benzoyls) β L thymus pyrimidines; by raw material 3; 5 dioxies carry out chloro sugar reaction under acidic catalyst effect to 2 deoxidation α of methyl benzoyl, β L furan first glycosides and organic solvent mixing; the thymus pyrimidine for adding hydroxyl protection carries out glycosylation reaction; post-treated, it is refining to obtain product, it is characterised in that：In chloro sugar course of reaction, the thymus pyrimidine of hydroxyl protection when raw materials quality content is less than 20%, is added, while carrying out the reaction of chloro sugar and glycosylation reaction, one-step method prepares 3 ', 5 ' dioxies (4 pairs of methyl benzoyls) β L thymus pyrimidines.The preparation method of the present invention is simple, low production cost, high income, is suitable for large-scale production.
Description
Technical field
The invention belongs to organic compound synthesis and preparing technical field, 3 ', 5 '-two-oxygen-(4- is to methyl to be related to one kind
Benzoyl)-β-L- thymus pyrimidines preparation method.
Technical background
The preparation method of 3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidines is typically using classical chlorine
In generation, is prepared by sugared glycosidation：I.e. using chloro sugar and the thymus pyrimidine that protects, under acidic catalyst effect, reaction is obtained；
Chloro sugar adopts 3,5-, bis--oxygen-to methyl benzoyl -2- deoxidation-α, β-L- furan first glycosides（Isomer proportion about 1:1）With chlorine
Changing hydrogen, preparation is reacted in acetic acid solution.The advantage of the method is can to obtain required beta isomer with high yield.But
Preparing chloro sugar process, the relatively low 60-65% of yield.
CN101415719A discloses a kind of system of 3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidines
Preparation Method：With the chloro- bis--oxygen of 3,5- of 1--methyl benzoyl -2- deoxidation-L- ribofuranoses and thymus pyrimidine are prepared as raw material
3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidines, yield 82.8%, prepare the yield 60 of chloro sugar～
65%.
Sivets, Grigorii G is in Nucleosides, Nucleotides and Nucleic Acids; vol.
26; nb. 10-12; (2007);In p1241 1244, it was recently reported that adopt 3,5-, bis--oxygen-de- to methyl benzoyl -2-
Oxygen-α, β-L- furan first glycosides and thymus pyrimidine are raw material, and trimethyl silicon substrate trifluoromethanesulfonic acid is catalyst, prepare 3 ', 5 '-two-
The method of oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidines, yield 60%.Due to without chloro sugar step, therefore obtaining
The α in product：β=1:2.6.Can only be purified with column chromatography and obtain pure β products.
It can be seen that, in above-mentioned prior art there is chloro sugar preparation process, low yield in two-step method disclosed in CN101415719A
The shortcomings of；The preparation method that Sivets, Grigorii G is provided, process is simple, it is to avoid prepared by yield low chloro sugar
Journey, but the low shortcoming of product yield is equally existed, and therefore technique is prepared without intermediate product chloro sugar, the product for obtaining
Middle β selectivity of product is poor, and post processing is complicated.
Content of the invention
The purpose of the present invention is for the above-mentioned problems in the prior art, there is provided a kind of 3 ', 5 '-two-oxygen-(4- pair
Methyl benzoyl)-β-L- thymus pyrimidines preparation method, this method by change process route by chloro sugar preparation process and
Two step of glycosylation reaction is combined into single step reaction, simplifies reactions steps, shortens the response time, promotes entering for chloro sugar reaction
OK, the decomposition of unstable intermedium chloro sugar is reduced, product yield is improve, beta comfiguration product assay is high in product, and omits
The post processing link of first step chloro sugar reaction, reduces the discharge of waste water, solvent slop, meets green chemistry requirement,
Suitable industrialized production.
In existing process, 3,5-, bis--oxygen-to methyl benzoyl -2- deoxidation-α is being adopted, β-L- furan first glycosides is raw material
During preparing chloro- 3,5-, the bis--oxygen of 1--to methyl benzoyl -2- deoxidation-L- ribofuranoses, i.e. chloro sugar preparation process
Yield is relatively low.Response analysises are tracked through HPLC, reason is that the reaction is reversible reaction, and a large amount of raw material reactions are not complete, and
Chloro- 3,5-, the bis--oxygen of 1- for arriving-unstable to methyl benzoyl -2- deoxidation-L- ribofuranoses, if extend the response time can divide
Solution, makes yield lower.
Technical solution of the present invention is：The present invention is improved on the basis of CN101415719A, former technique be first with 3,
Bis--oxygen of 5--to methyl benzoyl -2- deoxidation-α, β-L- furan first glycosides are that raw material prepares chloro- 3,5-, the bis--oxygen of 1--to methylbenzene
Formoxyl -2- deoxidation-L- ribofuranoses, then with chloro- 3,5-, the bis--oxygen of 1--to methyl benzoyl -2- deoxidation-L- ribofuranoses
It is that raw material prepares 3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidines with thymus pyrimidine.By two in the present invention
Individual step is merged into a step and is carried out, and first 3,5-, the bis--oxygen of addition in a kettle.-to methyl benzoyl -2- deoxidation-α, β-L- furans
First of muttering glycosides, solvent, are subsequently adding acidic catalyst, when raw materials quality content is less than 20%, add the thymus pyrimidine of hydroxyl protection
Reacted.Such advantage is chloro sugar（It is the chloro- bis--oxygen of 3,5- of intermediate product 1--to toluyl of this reaction
Base -2- deoxidation-L- ribofuranoses）Preparation process and glycosylation reaction are carried out simultaneously, due to intermediate product chloro sugar glycosylation
Reaction is consumed, and makes the chemical equilibrium of chloro sugar reaction continue, to the direction movement of intermediate product chloro sugar, to promote chloro sugar reaction
Carrying out, improve feed stock conversion, it is to avoid because intermediate product 1- chloro- 3,5-, bis--oxygen-to methyl benzoyl -2- deoxidations -
L- ribofuranoses decompose the yield for causing to be reduced, and eliminates last handling process prepared by chloro sugar.Preparation method of the present invention
Product yield can reach 80%, while being intermediate because employing chloro sugar, make the beta comfiguration ratio of product very high, its ratio beta：α
Up to 15:1.
The preparation method of one kind 3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidines of the invention is：Will
Raw material 3, bis--oxygen of 5--to methyl benzoyl -2- deoxidation-α, β-L- furan first glycosides and organic solvent mixing, in acidic catalyst
Chloro sugar reaction is carried out under effect, and the thymus pyrimidine for adding hydroxyl protection carries out glycosylation reaction, post-treated, be refining to obtain
Product, it is characterised in that：In chloro sugar course of reaction, when raw materials quality content is less than 20%, add the thymus of hydroxyl protection phonetic
Pyridine, while the reaction of chloro sugar and glycosylation reaction is carried out, one-step method preparation 3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-
L- thymus pyrimidines.
Described organic solvent is：One or two mixing, preferably methyl tertiary butyl ether(MTBE) in methyl tertiary butyl ether(MTBE), chloroform
Mix with chloroform；
Described acidic catalyst is：Hydrogen chloride gas, hydrogen chloride acetic acid solution, Hydrochloride/ethyl acetate or chlorination
Hydrogen dichloromethane solution.
Described 3,5-, bis--oxygen-to methyl benzoyl -2- deoxidation-α, β-L- furan first glycosides：Organic solvent：Catalyst：
The mass ratio of the thymus pyrimidine of hydroxyl protection is 1：3～20：0.1～0.5：0.5～5, wherein, preferably 1：8.35：0.332：
1.17.
The thymus pyrimidine preparation method of described hydroxyl protection is：Thymus pyrimidine, hexamethyldisiloxane, ammonium sulfate and first
Benzene mixes, and heats up, and flow back 4h, is cooled to 70～80 DEG C, is concentrated into without hexamethyldisiloxane, obtains the thymus of hydroxyl protection
Pyrimidine.
The preparation method of one kind 3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidines of the invention, step
As follows：
1）The thymus pyrimidine for preparing hydroxyl protection is standby；
2）Chloro sugar and glycosylation reaction：By 3,5-, bis--oxygen-to methyl benzoyl -2- deoxidation-α, β-L- furan first glycosides
Mix with organic solvent, stirring and dissolving is cooled to 0～50 DEG C, add acidic catalyst, carry out chloro sugar reaction, raw materials quality
When content is less than 20%, step 1 is added）The thymus pyrimidine of the hydroxyl protection of preparation, 0～50 DEG C of stirring reaction contain to raw materials quality
Amount is less than 1%, and reaction terminates, and obtains crude product reactant liquor；
3）It is quenched and reacts to obtain crude product：To in above-mentioned crude product reactant liquor, Deca dehydrated alcohol and deionized water are quenched respectively
Reaction, post processing obtain crude product；
4）Refined：Crude product is added in 95% ethanol, is warming up to 60～70 DEG C of 1～5h of stirring, and less than 70 DEG C are concentrated into
Dry, it is then added in 95% ethanol, is warming up to 60～70 DEG C of dispersed with stirring 1h, is cooled to 0～5 DEG C of 0.5～5h of stirring, sucking filtration is done
Dry 3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidine products.
Step 2）In, described raw materials quality content is raw material 3, bis--oxygen of 5--to methyl benzoyl -2- deoxidation-α, and β -
The content of L- furan first glycosides.
Step 2）In, preferably 20～25 DEG C of the sugared and glycosylation reaction temperature of chloro.
Step 3）In, described dehydrated alcohol and deionized water consumption, respectively raw material 3, bis--oxygen of 5--to methylbenzene first
0.05～5 times and 0.1 ~ 10 times, preferably 0.2 times and 0.4 times of acyl group -2- deoxidation-α, β-L- furan quality.
Described post processing, method are that stratification, organic layer are concentrated in salt acid elution, plus 10% sodium carbonate liquor with after
Extremely dry.
Described hydrochloric acid and 10% sodium carbonate liquor consumption, respectively raw material 3, bis--oxygen of 5--de- to methyl benzoyl -2-
1～10 times and 1 ~ 15 times of oxygen-α, β-L- furan first glycosides quality；Described concentration of hydrochloric acid scope is 0.01～10mol/L, preferably
0.2～0.3 mol/L.
Step 4）In twice 95% amount of alcohol added be 2～10 times of crude product quality.
The preparation method of one kind 3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidines of the invention, relative
In prior art, its advantage is：
1）Chloro sugar preparation process and two step of glycosylation reaction are combined into single step reaction, reactions steps are simplified, is shortened
Response time, and the post processing link of first step chloro sugar reaction is eliminated, the discharge of waste water, solvent slop is reduced, is met green
Colour chemistry demand for development, is suitable for industrialized production.
2）Chloro sugar preparation process and glycosylation reaction are carried out simultaneously, as intermediate product chloro sugar is disappeared by glycosylation reaction
Consumption, makes the chemical equilibrium of raw material reaction continue, to the direction movement of intermediate product chloro sugar, to promote the carrying out of chloro sugar reaction, keep away
Exempt from, because the yield that intermediate product chloro sugar decomposition is caused reduces, to improve feed stock conversion, the inventive method yield is reachable
80%, and two step yield of traditional handicraft only about 50%.
Description of the drawings
Hydrogen nuclear magnetic resonance spectrograms of the Fig. 1 for 1 product of the embodiment of the present invention
Nuclear magnetic resonance, NMR charcoal spectrograms of the Fig. 2 for 1 product of the embodiment of the present invention.
Specific embodiment
Technical solution of the present invention and beneficial effect are described, examination used in following examples below by specific embodiment
Agent is commercially available.
Embodiment 1
Prepare 3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidines to concretely comprise the following steps：
1）Prepare the thymus pyrimidine of hydroxyl protection：250mL adds 36 g thymus pyrimidines in the there-necked flask with reflux condensing tube,
The hexamethyldisiloxane of 63g, the toluene of the ammonium sulfate and 31g of 0.6g, mixing, after nitrogen displacement three times, heat up, and flow back 4h,
75 DEG C are cooled to, are concentrated, and, hexamethyldisiloxane is taken out of by steaming toluene, remaining concentration with 100g toluene band solvent twice
Liquid is sampled, and to testing result without hexamethyldisiloxane, obtains the thymus pyrimidine 78g of hydroxyl protection.
2）Chloro sugar and glycosylation reaction：Bis--the oxygen of 3,5--to methyl benzoyl -2- of 100g is added in 2L there-necked flasks
The chloroform of deoxidation-α, β-L- furan first glycosides, 125g methyl tertiary butyl ether(MTBE)s and 710g, stirring and dissolving are cooled to 5 DEG C, are slowly added to
33.2g（3.5 equivalent）Hydrogen chloride gas, are carried out chloro sugar reaction, are detected by HPLC, when raw materials quality content is less than 20%, plus
Enter step 1）The thymus pyrimidine 78g of the hydroxyl protection of preparation, 5 DEG C of stirring reactions, sampling HPLC detection raw materials quality contents after 3h
0.72%, reaction terminates, and obtains crude product reactant liquor.
3）It is quenched and reacts to obtain crude product：12.5g dehydrated alcohol and 20g are successively slowly added dropwise in above-mentioned crude product reactant liquor
Deionized water is quenched reaction, after adding 450 g of the hydrochloric acid washing 40min of 0.24mol/L, is neutralized with 10% sodium carbonate liquor 650g,
After stratification, organic layer is washed once, merges water layer chloroform back extraction twice once, by chloroform and the organic layer of stratification
Mixing, is concentrated to dryness, obtains crude product.
4）Refined：Crude product is added in 95% ethanol of 600g, is warming up to 60 DEG C of stirring 1h, is concentrated to dryness, is then added to
In 95% ethanol of 600g, 60 DEG C of dispersed with stirring 1h are warming up to, are cooled to 0～5 DEG C of stirring 0.5h, sucking filtration, dry 3 ', 5 '-two-
Oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidine product 100.8g, detects beta comfiguration purity 99.08%, product by HPLC
Yield is 80.9%.
Embodiment 2
1）Prepare the thymus pyrimidine of hydroxyl protection：With embodiment 1.
2）Chloro sugar and glycosylation reaction：Bis--the oxygen of 3,5--to methyl benzoyl -2- of 100g is added in 2L there-necked flasks
The chloroform of deoxidation-α, β-L- furan first glycosides, 125g ether and 175g, stirring and dissolving are cooled to 22 DEG C, are slowly introducing 475g contents
6% hydrogen chloride acetic acid solution（3 equivalents）, chloro sugar reaction is carried out, is detected by HPLC, when raw materials quality content is less than 20%,
Add step 1）The thymus pyrimidine 78g of the hydroxyl protection of preparation, 20 DEG C of stirring reactions, sampling detection raw materials quality content 1% after 3h
When, reaction terminates, and obtains crude product reactant liquor.
3）It is quenched and reacts to obtain crude product：5g dehydrated alcohol is successively slowly added dropwise in above-mentioned crude product reactant liquor and 10g goes
Ionized water is quenched reaction, after adding 1050 g of the hydrochloric acid washing 40min of 0.1mol/L, is neutralized with 10% sodium carbonate liquor 350g, quiet
After putting layering, organic layer is washed once, merges water layer chloroform back extraction twice once, the organic layer of chloroform and stratification is mixed
Close, be concentrated to dryness, obtain crude product.
4）Refined：Crude product is added in 95% ethanol of 200g, is warming up to 65 DEG C of stirring 1h, is concentrated to dryness, is then added to
In 95% ethanol of 200g, 65 DEG C of dispersed with stirring 1h are warming up to, are cooled to 3 DEG C of stirring 0.5h, sucking filtration, dry 3 ', 5 '-two-oxygen-
By HPLC, (4- is to methyl benzoyl)-β-L- thymus pyrimidine product 104.6g, detect that β purity 99.02%, product yield are
84%.
Embodiment 3
1）Prepare the thymus pyrimidine of hydroxyl protection：With embodiment 1.
2）Chloro sugar and glycosylation reaction：Bis--the oxygen of 3,5--to methyl benzoyl -2- of 100g is added in 2L there-necked flasks
The dichloromethane of deoxidation-α, β-L- furan first glycosides, 50g methyl tertiary butyl ether(MTBE)s and 710g, stirring and dissolving are cooled to 45 DEG C, slowly
It is passed through 11.37g（1.2 equivalent）Hydrogen chloride gas, are carried out chloro sugar reaction, are detected by HPLC, and raw materials quality content is less than 20%
When, add step 1）The thymus pyrimidine 78g of the hydroxyl protection of preparation, 40 DEG C of stirring reactions, sampling HPLC detection raw material matter after 3h
Amount content 0.72%, reaction terminates, and obtains crude product reactant liquor.
3）It is quenched and reacts to obtain crude product：200g dehydrated alcohol and 20g are successively slowly added dropwise in above-mentioned crude product reactant liquor
Deionized water is quenched reaction, after adding 45 g of the hydrochloric acid washing 40min of 10mol/L, is neutralized with 10% sodium carbonate liquor 650g, quiet
After putting layering, organic layer is washed once, merges water layer chloroform back extraction twice once, the organic layer of chloroform and stratification is mixed
Close, be concentrated to dryness, obtain crude product.
4）Refined：Crude product is added in 95% ethanol of 400g, is warming up to 70 DEG C of stirring 1h, is concentrated to dryness, is then added to
In 95% ethanol of 400g, 70 DEG C of dispersed with stirring 1h are warming up to, are cooled to 5 DEG C of stirring 0.5h, sucking filtration, dry 3 ', 5 '-two-oxygen-
By HPLC, (4- is to methyl benzoyl)-β-L- thymus pyrimidine product 93.35g, detect that β purity 99.16%, product yield are
75%.
Comparative example
Using existing process, the sugared preparation process of chloro and glycosylation reaction are carried out in two steps.
1）Prepare the thymus pyrimidine of hydroxyl protection：With embodiment 1.
2）Chloro sugar and glycosylation reaction：Bis--the oxygen of 3,5--to methyl benzoyl -2- of 100g is added in 2L there-necked flasks
The acetic acid of deoxidation-α, β-L- furan first glycosides, 125g methyl tertiary butyl ether(MTBE)s and 710g, stirring and dissolving are cooled to 5 DEG C, are slowly introducing
42.7g（4.5 equivalent）Hydrogen chloride gas.In 5 DEG C of stirring reactions 2h, filter.Washed with t-butyl methyl ether, vacuum drying is obtained
Chloro- 3,5-, the bis--oxygen of 1--to methyl benzoyl -2- deoxidation-α, β-L- ribofuranoses, 60.6g, yield 59.7%.
Add 100g chloroforms, chloro- 3,5-, the bis--oxygen of 60.6g--to methyl benzoyl -2- deoxidation-α in reaction bulb, β -
L- ribofuranoses, the thymus pyrimidine of the hydroxyl protection for preparing, 5 DEG C of stirring 3h, system clear detect raw materials quality content
0.72%, reaction terminates, and obtains crude product reactant liquor.
3）It is quenched and reacts to obtain crude product：12.5g dehydrated alcohol and 20g are successively slowly added dropwise in above-mentioned crude product reactant liquor
Deionized water is quenched reaction, after adding 450 g of the hydrochloric acid washing 40min of 0.24mol/L, is neutralized with 10% sodium carbonate liquor 650g,
After stratification, organic layer is washed once, merges water layer chloroform back extraction twice once, by chloroform and the organic layer of stratification
Mixing, is concentrated to dryness, obtains crude product.
4）Refined：Crude product is added in 95% ethanol of 300g, is warming up to 65 DEG C of stirring 1h, is concentrated to dryness, is then added to
In 95% ethanol of 300g, 65 DEG C of dispersed with stirring 1h are warming up to, are cooled to 5 DEG C of stirring 0.5h, sucking filtration, dry 3 ', 5 '-two-oxygen-
By HPLC, (4- is to methyl benzoyl)-β-L- thymus pyrimidine product 63.3g, detect that β purity 99.36%, product yield are
85%.Two step gross production rates 50.7%.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (6)
1. the preparation method of 3 ', 5 '-two-oxygen of one kind-(4- is to methyl benzoyl)-β-L- thymus pyrimidines, by raw material 3,5- bis--
Oxygen-and to methyl benzoyl -2- deoxidation-α, β-L- furan first glycosides and organic solvent mixing, carry out under acidic catalyst effect
Chloro sugar reaction, the thymus pyrimidine for adding hydroxyl protection carries out glycosylation reaction, post-treated, is refining to obtain product, and which is special
Levy and be：In chloro sugar course of reaction, the thymus pyrimidine of hydroxyl protection when raw materials quality content is less than 20%, is added, while carrying out
The reaction of chloro sugar and glycosylation reaction, one-step method prepare 3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidines；
Described organic solvent is methyl tertiary butyl ether(MTBE) or one or two mixing in chloroform；
Described acidic catalyst is hydrogen chloride gas, hydrogen chloride acetic acid solution, Hydrochloride/ethyl acetate or hydrogen chloride two
Chloromethanes solution；
Described 3,5-, bis--oxygen-to methyl benzoyl -2- deoxidation-α, β-L- furan first glycosides：Organic solvent：Catalyst：Hydroxyl
The mass ratio of the thymus pyrimidine of protection is 1：3～20：0.1～0.5：0.5～5；
The thymus pyrimidine preparation method of described hydroxyl protection is：Thymus pyrimidine, hexamethyldisiloxane, ammonium sulfate and toluene are mixed
Close, heat up, flow back 4h, is cooled to 70～80 DEG C, is concentrated into without hexamethyldisiloxane, and the thymus for obtaining hydroxyl protection are phonetic
Pyridine.
2. preparation method according to claim 1, it is characterised in that step is as follows：
1）The thymus pyrimidine for preparing hydroxyl protection is standby；
2）Chloro sugar and glycosylation reaction：By 3,5-, bis--oxygen-to methyl benzoyl -2- deoxidation-α, β-L- furan first glycosides and molten
Agent mixes, and stirring and dissolving is cooled to 0～50 DEG C, adds hydrogen chloride gas, carries out chloro sugar reaction, and raw materials quality content is less than
When 20%, step 1 is added）The thymus pyrimidine of the hydroxyl protection of preparation, 0～50 DEG C of stirring reaction to raw materials quality content are less than 1%,
Reaction terminates, and obtains crude product reactant liquor；
3）It is quenched and reacts to obtain crude product：To in above-mentioned crude product reactant liquor, Deca dehydrated alcohol and deionized water are quenched instead respectively
Should, post processing obtains crude product；
4）Refined：Crude product is added in 95% ethanol, is warming up to 60～70 DEG C of 1～5h of stirring, and less than 70 DEG C are concentrated to dryness, then
It is added in 95% ethanol, is warming up to 60～70 DEG C of dispersed with stirring 1h, be cooled to 0～5 DEG C of 0.5～5h of stirring, sucking filtration is dry
3 ', 5 '-two-oxygen-(4- is to methyl benzoyl)-β-L- thymus pyrimidine products.
3. preparation method according to claim 2, it is characterised in that：Step 2）In, described raw materials quality content is 3,5-
Two-oxygen-to methyl benzoyl -2- deoxidation-α, the content of β-L- furan first glycosides.
4. preparation method according to claim 2, it is characterised in that：Step 3）In, described dehydrated alcohol and deionized water
Consumption, respectively raw material 3, bis--oxygen of 5--to methyl benzoyl -2- deoxidation-α, 0.05～5 times and 0.1 of β-L- furan quality
~ 10 times.
5. preparation method according to claim 2, it is characterised in that：Step 3）In, described post processing, method are salt pickling
Wash, plus in 10% sodium carbonate liquor with after, stratification, organic layer are concentrated to dryness.
6. preparation method according to claim 2, it is characterised in that：Step 4）In twice 95% amount of alcohol added be thick product
2～10 times of amount of substance.
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