CN103172552B - 4-hydroxy-2-oxo-1-pyrrolidine acetamide racemate crystal I and preparation method thereof - Google Patents
4-hydroxy-2-oxo-1-pyrrolidine acetamide racemate crystal I and preparation method thereof Download PDFInfo
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- CN103172552B CN103172552B CN201310099007.9A CN201310099007A CN103172552B CN 103172552 B CN103172552 B CN 103172552B CN 201310099007 A CN201310099007 A CN 201310099007A CN 103172552 B CN103172552 B CN 103172552B
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- 239000013078 crystal Substances 0.000 title claims abstract description 53
- IHLAQQPQKRMGSS-UHFFFAOYSA-N oxiracetam Chemical class NC(=O)CN1CC(O)CC1=O IHLAQQPQKRMGSS-UHFFFAOYSA-N 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title abstract description 12
- SUBDBMMJDZJVOS-DEOSSOPVSA-N esomeprazole Chemical class C([S@](=O)C1=NC2=CC=C(C=C2N1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-DEOSSOPVSA-N 0.000 claims description 52
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 5
- 238000002329 infrared spectrum Methods 0.000 claims description 4
- 238000010521 absorption reaction Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 abstract description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 10
- 238000001914 filtration Methods 0.000 abstract description 7
- 239000002904 solvent Substances 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 230000004048 modification Effects 0.000 description 46
- 238000012986 modification Methods 0.000 description 46
- 229960004770 esomeprazole Drugs 0.000 description 43
- 230000015572 biosynthetic process Effects 0.000 description 27
- 239000012043 crude product Substances 0.000 description 15
- 239000000126 substance Substances 0.000 description 14
- 239000000843 powder Substances 0.000 description 12
- 238000001556 precipitation Methods 0.000 description 8
- 238000001291 vacuum drying Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- -1 acyl thanomin Chemical group 0.000 description 6
- 238000004062 sedimentation Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 229960000935 dehydrated alcohol Drugs 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 238000002411 thermogravimetry Methods 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical class NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 description 2
- 238000001069 Raman spectroscopy Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000003729 cation exchange resin Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 2
- 229950004354 phosphorylcholine Drugs 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SUBDBMMJDZJVOS-XMMPIXPASA-N (R)-omeprazole Chemical compound C([S@@](=O)C=1NC2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-XMMPIXPASA-N 0.000 description 1
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- YQGDEPYYFWUPGO-UHFFFAOYSA-N gamma-amino-beta-hydroxybutyric acid Chemical class [NH3+]CC(O)CC([O-])=O YQGDEPYYFWUPGO-UHFFFAOYSA-N 0.000 description 1
- 231100000652 hormesis Toxicity 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 229960001227 oxiracetam Drugs 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 229960004526 piracetam Drugs 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
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- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to 4-hydroxy-2-oxo-1-pyrrolidine acetamide racemate crystal I which is prepared according to the following steps of: dissolving a crude 4-hydroxy-2-oxo-1-pyrrolidine acetamide racemate product into a micromolecular alcohol solvent till supersaturation; heating at 38-42 DEG C, and overnight stirring to obtain suspended deposits; and filtering and drying to obtain a crystal. The 4-hydroxy-2-oxo-1-pyrrolidine acetamide racemate crystal I disclosed by the invention has high purity of 99.5% and achieves outstanding curative effect on curing corresponding diseases by being used for a drug; the preparation method of the 4-hydroxy-2-oxo-1-pyrrolidine acetamide racemate crystal I has the advantages of simpleness, moderate control condition and low production cost; and the prepared 4-hydroxy-2-oxo-1-pyrrolidine acetamide racemate crystal I has the advantages of high purity of 99.5% and ideal yield of 90% and is very suitable for large-scale industrialized production.
Description
The present invention is application number is 201110230079.3, and the applying date is on 08 11st, 2011, and denomination of invention is the divisional application of " Esomeprazole racemic modification crystal formation I and preparation method thereof ".
Technical field
The present invention relates to Esomeprazole medicine, be specifically related to Esomeprazole racemic modification crystal formation I and preparation method thereof.
Background technology
Esomeprazole is nootropic agents of new generation, pyrrolidinone compounds (ring GABOB) derivative, piracetam analogue, Phosphorylcholine and the synthesis of adjacent acyl thanomin can be promoted, promote brain metabolism, there is hormesis by hemato encephalic barrier to specificity central nervous pathway, improve intelligence and memory.To cerebro-vascular diseases, brain injury, brain tumor (postoperative), intracranial infection, dementia, brain degenerative disease etc., there is good efficacy.Be applicable to memory that the diseases such as light moderate vascular dementia, senile dementia and cerebral trauma cause and disturbance of intelligence.Esomeprazole was synthesized in 1974 than Qie Mu company by Italian SmithKline first, listing in 1987, can promote the synthesis of Phosphorylcholine and phosphatidyl ethanolamine, promotes brain metabolism, to remembering, concentrating of especially thinking is better than piracetam, and toxicity is little.The raceme that Esomeprazole is made up of two kinds of isomer (S)-Esomeprazoles and (R)-Esomeprazole.Its chemistry Esomeprazole by name.
The synthetic method of Esomeprazole, the preparation method of injection formulation and goods, dispersible tablet and preparation method thereof all have document and openly reported.But there is no the relevant report of Esomeprazole racemic modification crystal formation at present.
Summary of the invention
The object of the present invention is to provide Esomeprazole racemic modification crystal formation I, its purity is high, medicinal curative effect good.
Also do not have the relevant report of Esomeprazole racemic modification crystal formation at present, contriver is by the Esomeprazole racemic modification crystal formation called after Esomeprazole racemic modification crystal formation I in this patent.
Another object of the present invention is to the preparation method providing above-mentioned Esomeprazole racemic modification crystal formation I, the Esomeprazole racemic modification crystal formation I foreign matter content that this preparation method obtains is low, purity is high.
The object of the invention is to be realized by following technical measures:
Esomeprazole racemic modification crystal formation I, is characterized in that: it is that 12.011,15.318,17.407,19.633,21.228,22.052,24.577,25.223,27.647,28.161,29.109,30.805,31.276,31.766,32.77,33.477,35.252,35.645,36.236,37.379,39.56,40.489,41.256,41.948,43.443,44.628 degree of places have diffraction peak at angle of diffraction 2 θ.
Esomeprazole racemic modification crystal formation I, is characterized in that: its have following d (
) value and relative intensity per-cent I (%) value express-X-ray powder diffraction data,
Esomeprazole racemic modification crystal formation I, is characterized in that: it has X-ray powder diffraction pattern as shown in Figure 1.
The infrared spectra that Esomeprazole racemic modification crystal formation I of the present invention produces demonstrates absorption peak in following wave number:
3426(cm
-1)、3330(cm
-1)、3276(cm
-1)、3235(cm
-1)、2931(cm
-1)、2876(cm
-1)、1665(cm
-1)、1593(cm
-1)、1480(cm
-1)、1452(cm
-1)、1428(cm
-1)、1320(cm
-1)、1272(cm
-1)、1220(cm
-1)、1078(cm
-1)、974(cm
-1)、941(cm
-1)、757(cm
-1)、702(cm
-1)、602(cm
-1)、517(cm
-1)、450(cm
-1)。
The preparation method of above-mentioned Esomeprazole racemic modification crystal formation I, is characterized in that: described method is carried out according to the following steps:
(1), Esomeprazole racemic modification crude product is dissolved in small molecular alcohol kind solvent, reaches supersaturation;
(2), at 38 ~ 42 DEG C heated and stirred is spent the night, and must suspend precipitation;
(3), filter, dry crystallisate.
In order to improve purity and the yield of obtained Esomeprazole racemic modification further, above-mentioned small molecular alcohol kind solvent is preferably Virahol; Above-mentioned whipping temp is preferably 40 DEG C, churning time is preferably 7h.
Specifically, the preparation method of above-mentioned Esomeprazole racemic modification crystal formation I, carries out according to the following steps:
(1), Esomeprazole racemic modification crude product is dissolved in Virahol, reaches supersaturation, have suspended substance to separate out;
(2), at 40 DEG C the above-mentioned supersaturated solution having suspended substance to separate out of heated and stirred, stir 7h, must suspend precipitation;
(3), filter, vacuum-drying obtains powder crystallization thing in 24 hours.
The present invention has following beneficial effect:
The purity of Esomeprazole racemic modification crystal formation I of the present invention is high, can reach 99.5%, evident in efficacy for treating corresponding illness in medicine; The preparation method of Esomeprazole racemic modification crystal formation I of the present invention is simple, control condition is gentle, low production cost, obtained Esomeprazole racemic modification crystal form purity is high, can reach 99.5%, ideal yield coefficient, can 90% be reached, very be applicable to large-scale industrial production.
Accompanying drawing explanation
Fig. 1 is the powder diagram of Esomeprazole racemic modification crystal formation I;
Fig. 2 is differential scanning calorimeter (DSC) figure of Esomeprazole racemic modification crystal formation I;
Fig. 3 is the Raman spectrogram of Esomeprazole racemic modification crystal formation I;
Fig. 4 is infrared spectra (IR) figure of Esomeprazole racemic modification crystal formation I;
Fig. 5 is thermogravimetric analysis (TG) figure of Esomeprazole racemic modification crystal formation I.
Embodiment
Below in conjunction with accompanying drawing, the present invention is described in further detail, but below illustrate and the present invention is not limited, any to distortion of the present invention and change, only otherwise depart from spirit of the present invention, the scope that claims of the present invention define all should be belonged to.
Embodiment 1
By 50mg4-hydroxy-2-oxo-1-pyrrolidine acetamide racemic modification dissolving crude product in anhydrous methanol, stirring is spent the night, and filter, solution left standstill is in moisture eliminator, and solvent flashing, obtains colourless transparent crystal, productive rate 82%, purity 99.4%.
Esomeprazole racemic modification crude product of the present invention synthesizes as follows, and its purity is 98.5%:
A glycine ethyl ester hydrochloride 139.6g joins in anhydrous diethyl ether 1100ml by (), ice-coldly pass into ammonia 27.2g and make glycine ethyl ester hydrochloride dissociate into glycine ethyl ester, wherein glycine ethyl ester hydrochloride: anhydrous diethyl ether: ammonia is 1mol: 1100ml: 1.6mol to-6 DEG C;
B () adds dehydrated alcohol 336ml in above-mentioned product, sodium bicarbonate 67.2g, dropping 4-chloro-3-hydroxyl-ethyl butyrate 166.6g, and described time for adding is 1.8 hours, reacts 22 hours at pH8, temperature are 72 DEG C;
C () filters, with the abundant wash filtrate of ethanol, concentrated, enriched material is water-soluble, then the ethyl acetate adding 7 times of filtrate weight carries out extracting, aqueous phase concentrates, column chromatography for separation; Finally add the ammoniacal liquor that mass percentage concentration is 23%, at 22 DEG C, react 4 hours obtained oxiracetam crude products, wherein the consumption of 23% ammoniacal liquor is 13 times of column chromatography for separation products weight;
Wherein glycine ethyl ester: sodium bicarbonate: 4-chloro-3-hydroxyl-ethyl butyrate=1: 0.8: 1, with molar ratio computing, the consumption of dehydrated alcohol is 5 times of sodium bicarbonate weight;
D (), with water dissolution above-mentioned obtained crude product, by 732# storng-acid cation exchange resin, is then neutralized by 711# strongly basic anion exchange resin and collects solution, concentrated; Described crude product: water=1 gram: 0.5 milliliter, described thick product: described storng-acid cation exchange resin=1 gram: 10 milliliters.
Embodiment 2
By 100mg4-hydroxy-2-oxo-1-pyrrolidine acetamide racemic modification dissolving crude product in 95% ethanol, stirring is spent the night, and filter, solution left standstill is in moisture eliminator, and solvent flashing, obtains colourless transparent crystal, productive rate 85%, purity 99.2%.
Embodiment 3
By 50mg4-hydroxy-2-oxo-1-pyrrolidine acetamide racemic modification dissolving crude product in Virahol, stirring is spent the night, and filter, solution left standstill is in moisture eliminator, and solvent flashing, obtains colourless transparent crystal, productive rate 87%, purity 99.2%.
Embodiment 4
50mg4-hydroxy-2-oxo-1-pyrrolidine acetamide racemic modification crude product is placed in anhydrous methanol, reach supersaturation, more suspended substance is had to occur, 38 DEG C of heated and stirred suspended substances, stir 10h, suspension sedimentation and filtration, vacuum-drying 24 hours, precipitation powder is Esomeprazole racemate crystal, productive rate 80%, purity 99.5%.
Embodiment 5
50mg4-hydroxy-2-oxo-1-pyrrolidine acetamide racemic modification crude product is placed in dehydrated alcohol, reach supersaturation, more suspended substance is had to occur, 40 DEG C of heated and stirred suspended substances, stirring is spent the night, suspension sedimentation and filtration, vacuum-drying 24 hours, precipitation powder is Esomeprazole racemate crystal, productive rate 80%, purity 99.3%.
Embodiment 6
50mg4-hydroxy-2-oxo-1-pyrrolidine acetamide racemic modification crude product is placed in Virahol, reach supersaturation, more suspended substance is had to occur, 40 DEG C of heated and stirred suspended substances, stir 7h, suspension sedimentation and filtration, vacuum-drying 24 hours, precipitation powder is Esomeprazole racemate crystal, productive rate 88%, purity 99.5%.
Embodiment 7
50mg4-hydroxy-2-oxo-1-pyrrolidine acetamide racemic modification crude product is placed in n-propyl alcohol, reach supersaturation, more suspended substance is had to occur, 42 DEG C of heated and stirred suspended substances, stir 12h, suspension sedimentation and filtration, vacuum-drying 20 hours, precipitation powder is Esomeprazole racemate crystal, productive rate 80%, purity 99.3%.
Embodiment 8
50mg4-hydroxy-2-oxo-1-pyrrolidine acetamide racemic modification crude product is placed in Virahol, reach supersaturation, more suspended substance is had to occur, 43 DEG C of heated and stirred suspended substances, stir 11h, suspension sedimentation and filtration, vacuum-drying 18 hours, precipitation powder is Esomeprazole racemate crystal, productive rate 90%, purity 99.2%.
Embodiment 9
50mg4-hydroxy-2-oxo-1-pyrrolidine acetamide racemic modification crude product is placed in propyl carbinol, reach supersaturation, more suspended substance is had to occur, 45 DEG C of heated and stirred suspended substances, stir 6h, suspension sedimentation and filtration, vacuum-drying 20 hours, precipitation powder is Esomeprazole racemate crystal, productive rate 80%, purity 99.4%.
The mensuration of embodiment 10 Esomeprazole racemic modification crystal formation I
Bruker D8Advance diffractometer is adopted to measure the powder diagram of the crystal type Esomeprazole racemic modification obtained in embodiment 1, condition determination is as follows: Cu K α, 40kV, 40mV is light source, step-length 0.12 °, sweep velocity 10 °/min, sweep limit 5 ~ 45 °, room temperature, in its x-ray diffractogram of powder, described crystal type Esomeprazole racemic modification crystal formation is 12.011 at angle of diffraction 2 θ, 15.318, 17.407, 19.633, 21.228, 22.052, 24.577, 25.223, 27.647, 28.161, 29.109, 30.805, 31.276, 31.766, 32.77, 33.477, 35.252, 35.645, 36.236, 37.379, 39.56, 40.489, 41.256, 41.948, 43.443, 44.628 there is diffraction peak at degree place, its X-ray powder diffraction figure as shown in Figure 1.
Crystal type Esomeprazole racemic modification of the present invention, the per-cent I of its x-ray diffractogram of powder 1 spacing d, Bragg angle (2 θ) and relative intensity expresses, as follows:
Fig. 1 is X ray powder figure, consistent with the coatings of the Esomeprazole racemic modification single crystal structural data simulation of CCDC report;
As shown in Figure 2, its endothermic transition temperature is at 171 DEG C for differential scanning calorimeter (DSC) figure of crystal type Esomeprazole racemic modification.
Crystal type Esomeprazole racemic modification Raman spectrogram as shown in Figure 3.
Crystal type Esomeprazole racemic modification thermogravimetric analysis figure as shown in Figure 5.
Crystal type Esomeprazole racemic modification infrared spectrogram as shown in Figure 4, wave number be 3426,3330,3276,3235,2931,2876,1665,1593,1480,1452,1428,1320,1272,1220,1078,974,941,757,702,602,517,450cm
-1there is absorption peak at place.
Claims (4)
1.4-hydroxy-2-oxo-1-pyrrolidine acetamide racemate crystal I, is characterized in that: it is in angle of diffraction 2
θbe that 12.011,15.318,17.407,19.633,21.228,22.052,24.577,25.223,27.647,28.161,29.109,30.805,31.276,31.766,32.77,33.477,35.252,35.645,36.236,37.379,39.56,40.489,41.256,41.948,43.443,44.628 degree of places have diffraction peak.
2. Esomeprazole racemate crystal I as claimed in claim 1, is characterized in that: it has following d() value and relative intensity per-cent I(%) value expresses-X-ray powder diffraction data,
。
3. Esomeprazole racemate crystal I as claimed in claim 1, is characterized in that: it has X-ray powder diffraction pattern as shown in Figure 1.
4. the Esomeprazole racemate crystal I as described in claim 1,2 or 3, its infrared spectra produced demonstrates absorption peak in following wave number:
3426（cm
-1）、3330（cm
-1）、3276（cm
-1）、3235（cm
-1）、2931（cm
-1）、2876（cm
-1）、1665（cm
-1）、1593（cm
-1）、1480（cm
-1）、1452（cm
-1）、1428（cm
-1）、1320（cm
-1）、1272（cm
-1）、1220（cm
-1）、1078（cm
-1）、974（cm
-1）、941（cm
-1）、757（cm
-1）、702（cm
-1）、602（cm
-1）、517（cm
-1）、450（cm
-1）。
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101693685A (en) * | 2009-09-30 | 2010-04-14 | 苏州浩波科技股份有限公司 | Method for preparing 4-hydroxylethylpyrrolidone-2-acetamide |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101693685A (en) * | 2009-09-30 | 2010-04-14 | 苏州浩波科技股份有限公司 | Method for preparing 4-hydroxylethylpyrrolidone-2-acetamide |
Non-Patent Citations (2)
| Title |
|---|
| Bandoli Giuliano et al.."Solid-state structure and conformation of the nootropic agent 4-hydroxy-2-oxo-1-pyrrolidineacetamide: x-ray and theoretical self-consistent field molecular orbital (SCF-MO) studies".《Chemical & * |
| Pharmaceutical Bulletin》.1985,第33卷(第10期),第4395-4401页. * |
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