CN105017183B - A kind of method for crystallising of pharmaceutical intermediate - Google Patents
A kind of method for crystallising of pharmaceutical intermediate Download PDFInfo
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- CN105017183B CN105017183B CN201510420347.6A CN201510420347A CN105017183B CN 105017183 B CN105017183 B CN 105017183B CN 201510420347 A CN201510420347 A CN 201510420347A CN 105017183 B CN105017183 B CN 105017183B
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- 238000000034 method Methods 0.000 title claims abstract description 25
- 239000012450 pharmaceutical intermediate Substances 0.000 title claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- 239000012043 crude product Substances 0.000 claims abstract description 15
- 238000002425 crystallisation Methods 0.000 claims abstract description 11
- 230000008025 crystallization Effects 0.000 claims abstract description 11
- 238000001035 drying Methods 0.000 claims abstract description 3
- 239000003960 organic solvent Substances 0.000 claims description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- 238000003756 stirring Methods 0.000 claims description 23
- 238000002156 mixing Methods 0.000 claims description 20
- 239000000706 filtrate Substances 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000013078 crystal Substances 0.000 claims description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 11
- 238000010792 warming Methods 0.000 claims description 10
- 239000012065 filter cake Substances 0.000 claims description 9
- 239000003208 petroleum Substances 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- 235000019441 ethanol Nutrition 0.000 claims description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 4
- 239000000543 intermediate Substances 0.000 claims description 2
- 238000000967 suction filtration Methods 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims 2
- 238000001914 filtration Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 12
- 238000007605 air drying Methods 0.000 description 8
- 150000002170 ethers Chemical class 0.000 description 7
- 238000010583 slow cooling Methods 0.000 description 7
- 238000010586 diagram Methods 0.000 description 5
- 238000000634 powder X-ray diffraction Methods 0.000 description 4
- 0 C[C@](*O[C@@]1COC(c2ccccc2)=O)([C@@]1OC(c1ccccc1)=O)F Chemical compound C[C@](*O[C@@]1COC(c2ccccc2)=O)([C@@]1OC(c1ccccc1)=O)F 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- OUKYMZJNLWKCSO-JXXFODFXSA-N C[C@@]([C@@H]([C@@H](COC(c1ccccc1)=O)O1)OC(c2ccccc2)=O)(C1=O)F Chemical compound C[C@@]([C@@H]([C@@H](COC(c1ccccc1)=O)O1)OC(c2ccccc2)=O)(C1=O)F OUKYMZJNLWKCSO-JXXFODFXSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/20—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention discloses a kind of method for crystallising of pharmaceutical intermediate, are related to chemical field.This method is by the way that successively by the step of dissolving, crystallization, growing the grain and drying, chemical compounds I is extracted from crude product solution for crude product.This method is easy to operate, and yield and purity are higher, low using cost of material, is suitble to industrialized production；Wherein, R group is Cl or Br.
Description
Technical field
The present invention relates to chemical field, more particularly to a kind of method for crystallising of pharmaceutical intermediate.
Background technology
Pharmaceutical intermediate chemical compounds I is a kind of halogenated tetrahydrofuran-compounds of 5-, is that one kind of prepare compound III is important
Pharmaceutical intermediate.
Wherein, R group is Cl or Br.
Pass through experiment and document report, it is known that reduction and halogenating reaction of the compounds Ⅳ through red aluminum have obtained one group
Mixture, wherein the configuration of only chemical compounds I is to react required in next step, and its isomers enters reaction in next step and then can
Generate impurity.It would therefore be desirable to take some measures and method, crystallization and purification is carried out to chemical compounds I, is contained so as to improve it
Amount lays the foundation for reaction in next step.
Wherein, R group is Cl or Br.
At present, there are no the method for crystallising that document report crosses chemical compounds I.
Invention content
It is an object of the invention to provide a kind of method for crystallising of completely new pharmaceutical intermediate chemical compounds I, pass through the crystallization side
Method removes isomer impurities, obtains the higher chemical compounds I of purity.
Wherein, R group is Cl or Br.
The purpose of the present invention can be achieved through the following technical solutions：
A kind of method for crystallising of pharmaceutical intermediate, the structural formula of the intermediate are as follows：
Wherein, R group is Cl or Br.
This method includes the following steps：
The first step, dissolving：Crude product is dissolved in organic solvent a, is warming up to dissolving, activated carbon is added in after dissolving and is taken off
Color filters while hot, collects filtrate；
Second step, crystallization：The filtrate temperature of collection is kept for 50~60 DEG C, adds in organic solvent b thereto to a small amount of crystalline substance
Body occurs；
Third walks, growing the grain, which includes three phases, as follows successively：
First stage is cooled to 30~50 DEG C while stirring in the mixed liquor, keeps the temperature 1~5 hour later, obtains
Mixed liquor a；
Second stage is cooled to -10~10 DEG C while stirring in the mixed liquor a, keeps the temperature 1~5 hour later, obtains
To mixed liquor b；
Phase III, warming while stirring is to 10~30 DEG C in the mixed liquor b, standing 10~20 hours, crystallization,
It filters；
4th step, it is dry：The filter cake obtained after suction filtration is washed using the mixed liquor of organic solvent a and organic solvent b
It washs, is dried after washing and obtain chemical compounds I；
Wherein, the organic solvent a is the organic solvent of alcohols or esters, the organic solvent b for ethers or
The organic solvent of alkanes.
In the preferred scheme of some technologies, organic solvent a for ethyl acetate, methanol, ethyl alcohol, one kind in isopropanol or
Several, preferable organic solvent a is ethyl acetate；Organic solvent b is petroleum ether, n-hexane, one or more of normal heptane, excellent
It is petroleum ether to select organic solvent b.
In some preferred technical solutions：In the first step, it is warming up to 60~80 DEG C and extremely dissolves, and m (chemical compounds I, g)：m
(activated carbon, g)=1：0.01~0.1.
In some technical solutions, in the first step and second step, m (crude product, g)：V (organic solvent a, mL)：V is (organic molten
Agent b, mL)=1：3~8：9~24；Further preferably, m (crude product, g)：V (organic solvent a, mL)：V (organic solvent b, mL)=
1：4~6：12~18.
In some preferred technical solutions, in third step, the cooling rate of first stage is 2~6 DEG C/min, second-order
The cooling rate of section is 1~3 DEG C/min, and the heating rate of phase III is 3~8 DEG C/min.
In some preferred technical solutions, in third step, the mixing speed of first stage is 150~200rpm, second
The mixing speed in stage is 70~90rpm, and the mixing speed of phase III is 40~60rpm.
In some technical solutions, in the 4th step, V (organic solvent a, mL)：V (organic solvent b, mL)=1：5~15, it is excellent
Select V (organic solvent a, mL)：V (organic solvent b, mL)=1：8~12.
In technical solution of the present invention, when R is Cl, the X-ray powder diffraction collection of chemical compounds I is 7.08,16.00 in 2 θ,
There is characteristic diffraction peak at 18.56,22.12,28.00,29.12, and the fusing point of chemical compounds I is 75.3~76.9 DEG C.
In technical solution of the present invention, when R is Br, the X-ray powder diffraction collection of chemical compounds I is 7.06,16.00 in 2 θ,
There is characteristic diffraction peak at 18.54,22.08,27.98,29.08, and the fusing point of chemical compounds I is 78.5~79.5 DEG C.
In 4th step of technical solution of the present invention, crystal drying condition is 35~40 DEG C of forced air dryings 10~15 hours.
Beneficial effects of the present invention：
The invention discloses a series of this method for crystallising, and not only production technology is easy, but also product yield is high, and purity is high,
Process costs also decrease.
Description of the drawings
Fig. 1 is the X-ray powder diffraction collection of chemical compounds I (R Br) that the method for the present invention is used to crystallize.
Fig. 2 is the X-ray powder diffraction collection of chemical compounds I (R Cl) that the method for the present invention is used to crystallize.
Specific embodiment
With reference to embodiment, the invention will be further described, and but the scope of the present invention is not limited thereto：
Chemical compounds I (R=Cl or Br) crude product can be used existing preparation method and obtain, used by the embodiment of the present invention 1~7
Chemical compounds I (R=Cl or Br) crude product purity is 75.6%, content of isomer 9.3%, moisture 0.01%.
Embodiment 1
Dissolving：13.23g chemical compounds Is crude product (R=Cl) is taken, adds in 50ml ethyl acetate thereto, adds in 0.5g activity
Charcoal after being warming up to 80 DEG C of stirring 30min, filters, collects filtrate while hot；
Crystallization：Filtrate slow cooling is added dropwise 200ml petroleum ethers and a small amount of crystal occurs thereto to 55 DEG C；
Growing the grain：First stage is stirred with the mixing speed of 190rpm in the solution for crystal occur so that the temperature of the solution
Degree is down to 30 DEG C, keeps the temperature 3 hours later；Second stage is again stirring for the solution with the mixing speed of 80rpm, and stirred
The temperature of the solution is made to be reduced to 0 DEG C during mixing, keeps the temperature 3 hours later；Phase III, with the speed of 50rpm again
The stirring solution so that the temperature of solution rises to 30 DEG C, stands 12 hours, crystallizes, and filters；Wherein, the drop of first stage
Warm speed is 2 DEG C/min, and the cooling rate of second stage is 2 DEG C/min, and the heating rate of phase III is 3 DEG C/min.
It is dry：Filter cake 11ml ethyl acetate/petroleum ethers (volume ratio 1：10) wash, solid in 40 DEG C of forced air drying 12h,
Obtain 9.36g white solids, yield 93.9%, purity 99.5%, isomers 0.15%.
The characteristic peak (2 θ values) of powder diagram comes across 7.08,16.00,18.56,22.12,28.00,29.12；Fusing point
It is 75.3~76.9 DEG C.
Embodiment 2
Dissolving：13.23g chemical compounds Is crude product (R=Br) is taken, adds in 45ml ethyl acetate thereto, adds in 0.6g activity
Charcoal after being warming up to 75 DEG C of stirring 30min, filters, collects filtrate while hot；
Crystallization：Filtrate slow cooling is added dropwise 190ml petroleum ethers and a small amount of crystal occurs thereto to 50 DEG C；
Growing the grain：First stage is stirred with the mixing speed of 200rpm in the solution for crystal occur so that the temperature of the solution
Degree is down to 40 DEG C, when keeping the temperature 2.5 later；Second stage is again stirring for the solution with the mixing speed of 80rpm, and stirred
The temperature of the solution is made to be reduced to -10 DEG C during mixing, keeps the temperature 3 hours later；It is phase III, another with the speed of 50rpm
Solution described in secondary stirring so that the temperature of solution rises to 30 DEG C, stands 12 hours, crystallizes, and filters；Wherein, first stage
Cooling rate is 3 DEG C/min, and the cooling rate of second stage is 1 DEG C/min, and the heating rate of phase III is 4 DEG C/min.
It is dry：Filter cake 11ml ethyl acetate/petroleum ethers (volume ratio 1：10) wash, solid in 40 DEG C of forced air drying 12h,
Obtain 9.11g white solids, yield 91.1%, purity 99.8%, isomers 0.12%.
The characteristic peak (2 θ values) of powder diagram comes across 7.06,16.08,18.54,22.00,27.98,29.08；Fusing point
It is 78.5~79.5 DEG C.
Embodiment 3
Dissolving：13.23g chemical compounds Is crude product (R=Cl) is taken, adds in 40ml methanol thereto, adds in 0.3g activated carbons, is risen
After temperature to 80 DEG C of stirring 30min, filter while hot, collect filtrate；
Crystallization：Filtrate slow cooling is added dropwise 160ml normal heptanes and a small amount of crystal occurs thereto to 55 DEG C；
Growing the grain：First stage is stirred with the mixing speed of 200rpm in the solution for crystal occur so that the temperature of the solution
Degree is down to 40 DEG C, when keeping the temperature 2.5 later；Second stage is again stirring for the solution with the mixing speed of 90rpm, and stirred
The temperature of the solution is made to be reduced to 10 DEG C during mixing, keeps the temperature 3.5 hours later；It is phase III, another with the speed of 60rpm
Solution described in secondary stirring so that the temperature of solution rises to 30 DEG C, stands 15 hours, crystallizes, and filters；Wherein, first stage
Cooling rate is 4 DEG C/min, and the cooling rate of second stage is 3 DEG C/min, and the heating rate of phase III is 5 DEG C/min.
It is dry：Filter cake 11ml Methanol/n-Heptanes (volume ratio 1：10) it washs, solid is obtained in 40 DEG C of forced air drying 12h
8.43g white solids, yield 84.3%, purity 98.0%, isomers 0.34%.
The characteristic peak (2 θ values) of powder diagram comes across 7.08,16.00,18.56,22.12,28.00,29.12；Fusing point
It is 75.3~76.9 DEG C.
Embodiment 4
Dissolving：13.23g chemical compounds Is crude product (R=Cl) is taken, adds in 40ml ethyl alcohol thereto, adds in 1.0g activated carbons, is risen
After temperature to 70 DEG C of stirring 30min, filter while hot, collect filtrate；
Crystallization：Filtrate slow cooling is added dropwise 200ml n-hexanes and a small amount of crystal occurs thereto to 50 DEG C；
Growing the grain：First stage is stirred with the mixing speed of 150rpm in the solution for crystal occur so that the temperature of the solution
Degree is down to 40 DEG C, when keeping the temperature 3 later；Second stage is again stirring for the solution with the mixing speed of 70rpm, and stirred
During the temperature of the solution is made to be reduced to 10 DEG C, later keep the temperature 2.5 hours；Phase III, with the speed of 30rpm again
The stirring solution so that the temperature of solution rises to 30 DEG C, stands 15 hours, crystallizes, and filters；Wherein, the drop of first stage
Warm speed is 6 DEG C/min, and the cooling rate of second stage is 3 DEG C/min, and the heating rate of phase III is 8 DEG C/min.
It is dry：Filter cake 11ml ethyl alcohol/n-hexane (volume ratio 1：10) it washs, solid is obtained in 35 DEG C of forced air drying 12h
8.86g white solids, yield 88.6%, purity 96.5%, isomers 0.56%.
The characteristic peak (2 θ values) of powder diagram comes across 7.08,16.00,18.56,22.12,28.00,29.12；Fusing point
It is 75.3~76.9 DEG C.
Embodiment 5
Dissolving：13.23g chemical compounds Is crude product (R=Br) is taken, adds in 40ml isopropanols thereto, adds in 1.0g activated carbons,
After being warming up to 75 DEG C of stirring 30min, filter while hot, collect filtrate；
Crystallization：Filtrate slow cooling is added dropwise 180ml n-hexanes and a small amount of crystal occurs thereto to 50 DEG C；
Growing the grain：First stage is stirred with the mixing speed of 150rpm in the solution for crystal occur so that the temperature of the solution
Degree is down to 40 DEG C, keeps the temperature 2 hours later；Second stage is again stirring for the solution with the mixing speed of 70rpm, and stirred
The temperature of the solution is made to be reduced to 10 DEG C during mixing, keeps the temperature 3 hours later；Phase III, with the speed of 40rpm again
The stirring solution so that the temperature of solution rises to 30 DEG C, stands 15 hours, crystallizes, and filters；Wherein, the drop of first stage
Warm speed is 5 DEG C/min, and the cooling rate of second stage is 2 DEG C/min, and the heating rate of phase III is 7 DEG C/min.
It is dry：Filter cake 11ml isopropanols/n-hexane (volume ratio 1：10) it washs, solid is obtained in 40 DEG C of forced air drying 12h
To 8.53g white solids, yield 85.3%, purity 97.1%, isomers 0.49%.
The characteristic peak (2 θ values) of powder diagram comes across 7.06,16.00,18.54,22.08,27.98,29.08；Fusing point
It is 78.5~79.5 DEG C.
6 comparative example of embodiment
13.23g chemical compounds Is crude product (R=Cl) is taken, adds in 50ml ethyl acetate thereto, adds in 0.5g activated carbons, heating
It to 70 DEG C of stirring 30min, filters while hot, filtrate slow cooling is added dropwise 200ml petroleum ethers, is slowly dropped to thereto to 50 DEG C
Room temperature is stirred overnight, and is filtered, and filter cake 10ml petroleum ethers, solid obtains 5.77g whites and consolidate in 40 DEG C of forced air drying 12h
Body, yield 57.7%, purity 90.3%, isomers 2.6%.
7 comparative example of embodiment
13.23g chemical compounds Is crude product (R=Br) is taken, adds in 40ml isopropanols thereto, 0.5g activated carbons is added in, is warming up to
It after 70 DEG C of stirring 30min, filters while hot, filtrate slow cooling is added dropwise 190ml n-hexanes, is slowly dropped to room thereto to 50 DEG C
Temperature is stirred overnight, and is filtered, and filter cake is washed with 10ml n-hexanes, and solid obtains 5.36g whites and consolidate in 40 DEG C of forced air drying 12h
Body, yield 53.6%, purity 90.1%, isomers 3.1%.
Claims (8)
1. a kind of method for crystallising of pharmaceutical intermediate, the structural formula of the intermediate are as follows：
Wherein, R group is Cl or Br, it is characterised in that：This method includes the following steps：
The first step, dissolving：Crude product is dissolved in organic solvent a, is warming up to dissolving, activated carbon is added in after dissolving and is decolourized, is taken advantage of
Heat filtering collects filtrate；
Second step, crystallization：The filtrate temperature of collection is kept for 50~60 DEG C, dropwise addition organic solvent b to a small amount of crystal goes out thereto
It is existing, obtain mixed liquor；
Third walks, growing the grain, which includes three phases, as follows successively：
First stage is cooled to 30~50 DEG C while stirring in the mixed liquor, keeps the temperature 1~5 hour later, is mixed
Liquid a；
Second stage is cooled to -10~10 DEG C while stirring in the mixed liquor a, keeps the temperature 1~5 hour later, is mixed
Close liquid b；
Phase III, to 10~30 DEG C, standing 10~20 hours crystallizes, and takes out for warming while stirring in the mixed liquor b
Filter；
4th step, it is dry：The filter cake obtained after suction filtration using the mixed liquor of organic solvent a and organic solvent b is washed, is washed
Drying obtains chemical compounds I after washing；
Wherein, the organic solvent a is one or more of ethyl acetate, methanol, ethyl alcohol, isopropanol, and described is organic
Solvent b is one or more of petroleum ether, n-hexane, normal heptane.
2. the method for crystallising of pharmaceutical intermediate according to claim 1, it is characterised in that：In the first step, it is warming up to 60~
80 DEG C extremely dissolve.
3. the method for crystallising of pharmaceutical intermediate according to claim 1, it is characterised in that：In third step, the first stage
Cooling rate is 2~6 DEG C/min, and the cooling rate of second stage is 1~3 DEG C/min, and the heating rate of phase III is 3~8
℃/min。
4. the method for crystallising of pharmaceutical intermediate according to claim 1, it is characterised in that：In third step, the first stage
Mixing speed is 150~200rpm, and the mixing speed of second stage is 70~90rpm, the mixing speed of phase III for 40~
60rpm。
5. the method for crystallising of pharmaceutical intermediate according to claim 1, it is characterised in that：When R is Cl, the X- of chemical compounds I
Ray powder diffraction has characteristic diffraction peak at 2 θ is 7.08,16.00,18.56,22.12,28.00,29.12.
6. the method for crystallising of pharmaceutical intermediate according to claim 1 or 5, it is characterised in that：When R is Cl, chemical compounds I
Fusing point is 75.3~76.9 DEG C.
7. the method for crystallising of pharmaceutical intermediate according to claim 1, it is characterised in that：When R is Br, the X- of chemical compounds I
Ray powder diffraction has characteristic diffraction peak at 2 θ is 7.06,16.00,18.54,22.08,27.98,29.08.
8. the method for crystallising of the pharmaceutical intermediate according to claim 1 or 7, it is characterised in that：When R is Br, chemical compounds I
Fusing point is 78.5~79.5 DEG C.
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| PA8855701A1 (en) * | 2008-12-23 | 2010-07-27 | NUCLEOSID ANALOGS | |
| AR091166A1 (en) * | 2012-05-29 | 2015-01-14 | Hoffmann La Roche | PROCESS FOR OBTAINING NUCLEOSID COMPOUNDS 2-DESOXI-2-FLUOR-2-METHYL-D-RIBOFURANOSIL |
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