CN118388366A - Novel preparation method of oseltamivir - Google Patents
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- CN118388366A CN118388366A CN202410505732.XA CN202410505732A CN118388366A CN 118388366 A CN118388366 A CN 118388366A CN 202410505732 A CN202410505732 A CN 202410505732A CN 118388366 A CN118388366 A CN 118388366A
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- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 title claims abstract description 32
- 229960003752 oseltamivir Drugs 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 9
- 238000010511 deprotection reaction Methods 0.000 claims abstract description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 16
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 10
- 239000003513 alkali Substances 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 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 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 4
- 238000012544 monitoring process Methods 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 150000001925 cycloalkenes Chemical class 0.000 abstract description 2
- -1 cycloolefin structure compound Chemical class 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract description 2
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 229910052698 phosphorus Inorganic materials 0.000 abstract description 2
- 239000011574 phosphorus Substances 0.000 abstract description 2
- 238000007363 ring formation reaction Methods 0.000 abstract description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical group NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 125000003158 alcohol group Chemical group 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- PGZUMBJQJWIWGJ-ONAKXNSWSA-N oseltamivir phosphate Chemical compound OP(O)(O)=O.CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 PGZUMBJQJWIWGJ-ONAKXNSWSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000003223 protective agent Substances 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 238000007142 ring opening reaction Methods 0.000 description 2
- 229940061367 tamiflu Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 208000002979 Influenza in Birds Diseases 0.000 description 1
- 102000005348 Neuraminidase Human genes 0.000 description 1
- 108010006232 Neuraminidase Proteins 0.000 description 1
- 229940123424 Neuraminidase inhibitor Drugs 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 206010064097 avian influenza Diseases 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000007275 deallylation reaction Methods 0.000 description 1
- 239000012351 deprotecting agent Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 208000037797 influenza A Diseases 0.000 description 1
- 208000037798 influenza B Diseases 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 229960002194 oseltamivir phosphate Drugs 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- JXOHGGNKMLTUBP-HSUXUTPPSA-N shikimic acid Chemical compound O[C@@H]1CC(C(O)=O)=C[C@@H](O)[C@H]1O JXOHGGNKMLTUBP-HSUXUTPPSA-N 0.000 description 1
- JXOHGGNKMLTUBP-JKUQZMGJSA-N shikimic acid Natural products O[C@@H]1CC(C(O)=O)=C[C@H](O)[C@@H]1O JXOHGGNKMLTUBP-JKUQZMGJSA-N 0.000 description 1
- 239000002911 sialidase inhibitor Substances 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a novel preparation method of oseltamivir, which comprises the steps of preparing a phosphorus ylide reagent through a novel cyclization process by using a compound I, further synthesizing a cycloolefin structure compound through a witting reaction, and obtaining oseltamivir as a synthesized cycloolefin deprotection agent. The beneficial effects of the invention are as follows: the invention provides a novel preparation method for synthesizing oseltamivir, which is favorable for further development of oseltamivir synthesis processes by technicians in the field, and is good in product selectivity, high in yield, high in chiral selectivity, high in product purity, convenient in product post-treatment, short in reaction route, simple to operate, high in product yield and purity, mild in reaction condition and suitable for industrial large-scale production.
Description
Technical Field
The invention relates to the technical field related to synthesis of medical intermediates, in particular to a preparation method of an oseltamivir intermediate.
Background
Oseltamivir phosphate is a highly potent, highly selective neuraminidase inhibitor developed by the american gilid science company and swiss rogowski pharmaceutical company, which was first marketed in the united states and swiss in 1999 and in china in 2004 under the trade name Tamiflu (Tamiflu). Clinically, the composition is mainly used for preventing and treating diseases caused by neuraminidase such as influenza A and B. Oseltamivir has been recognized as the most effective anti-avian influenza drug to date. Therefore, its synthesis is very important. Oseltamium Wei Huaxue: (3R, 4R, 5S) -4-acetamide-5-amino-3- (1-propoxy ethyl) -1-cyclohexene-1-carboxylic acid ethyl ester, the structure is shown as follows:
。
There are many literature and patent reports on the preparation method of oseltamivir, but most routes use expensive reagents and have high production cost. At present, the main route is to prepare oseltamivir key intermediates by taking (-) -shikimic acid as a raw material, and then to prepare oseltamivir through multi-step reactions.
The method mainly comprises the following steps:
route one, patent US5763483, document JournalofOrganicChemistry1998, 63, 4545-4550 is an open loop route for sodium azide, but the use of highly toxic and explosive sodium azide increases the production risk and yields are lower.
Route two, patent US6403824, literature JournalofOrganicChemistry2001, 66, 2044-2051) is an allylamine ring-opening route, the whole route uses two allylamines and two palladium carbon catalytic deallylation to prepare oseltamivir, the method needs to use expensive palladium catalyst, and the cost is high;
route three, literature OrganicProcessResearch & Development2004,8, 86-91 is a tert-butylamine, bis allylamine ring opening route, and the method uses expensive palladium catalyst, has more severe reaction conditions and higher production cost, and uses palladium acetate to remove allyl to prepare oseltamivir.
In summary, the existing route for preparing oseltamivir Wei Gongyi has various defects of harsh reaction conditions, higher production cost, poor safety and the like, so that the development of a simple, convenient and effective oseltamivir synthesis route with low cost, high yield and environmental friendliness has important scientific research significance and practical value.
Disclosure of Invention
Aiming at the defects, the invention aims to provide a preparation method of oseltamivir, which is characterized in that a new cyclization process is adopted, a phosphorus ylide reagent is prepared by a compound I, a cycloolefin structure compound is further synthesized by a witting reaction, and a synthesized cycloolefin removal protective agent is oseltamivir. .
1. The novel preparation method of oseltamivir is characterized by comprising the following steps of:
Dissolving a compound I in an organic solvent, adding an alkali reagent, gradually adding a catalyst triphenylphosphine, reacting for 30min at a low temperature of-20 to-10 ℃, then gradually heating to 20-30 ℃, continuing the reaction, monitoring the reaction by HPLC, detecting the termination of the reaction, and separating a product to obtain a compound II;
secondly, removing the protecting group of the product compound II obtained in the second step by adopting a deprotection agent to obtain a target compound III;
The specific reaction process flow is as follows:
。
Further, the solvent of the first reaction step is anhydrous diethyl ether.
Further, the alkali agent used in the first step is an ether solution of n-butyllithium, and the concentration of the n-butyllithium is 2.5mol/L.
Further, the amount of the alkali agent used in the first reaction is 1.5 to 2eq, preferably 2.0eq, of the compound I.
Further, the molar ratio of triphenylphosphine serving as a catalyst to the compound I in the first-step reaction is 1:1.
Further, the deprotection agent used in the second reaction step is trifluoroacetic acid.
Further, the trifluoroacetic acid is a solution using methanol as a solvent.
Further, the concentration of the deprotection agent sodium hydroxide/alcohol solution is 50-60 wt%.
Further, the molar ratio of the compound II to the deprotecting agent in the second reaction step is 1:1.
Further, the organic solvent used in the second reaction step is dichloromethane.
The compound I can be synthesized by various methods, for example, the compound I is prepared by a1, 3-dicarbonyl compound, an acetamido group is prepared by introducing an amino group between two carbonyl groups to react with acyl chloride, then chiral reduction is carried out on the carbonyl groups to form an alcohol group, then an ether bond and the amino group are introduced from the alcohol group, the amino group is protected by a protective agent, and the compound I with three chiral cores can be obtained.
The beneficial effects of the invention are as follows: 1. the invention provides a novel preparation method for synthesizing oseltamivir, which is favorable for further development of oseltamivir synthesis processes by technicians in the field, and is synthesized through witting reaction, so that the product selectivity is good, the yield is high, the chiral selectivity is high, the product purity is high, and the post-treatment of the product is convenient; 2. the invention has the advantages of short reaction route, simple operation, high product yield and purity, mild reaction conditions and suitability for industrialized large-scale production.
Drawings
FIG. 1 is a schematic illustration of the reaction scheme of the present invention;
fig. 2 is a schematic diagram of oseltamivir structure of the present invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Dissolving 23.2g (0.05 mol) of a compound I in 250ml of diethyl ether as an organic solvent under the protection of nitrogen, adding an ether solution (2.5 mol/L) of an alkali reagent n-butyllithium (0.1 mol), gradually adding a catalyst 0.05mol of triphenylphosphine, reacting for 30min at a low temperature of-20 to-10 ℃, then gradually heating to 20-30 ℃, continuing the reaction, monitoring the reaction by HPLC, detecting the end of the reaction, slowly dripping dry cyclohexane at the temperature of 0 ℃ for quenching the reaction, evaporating the solvent, adding 100ml of chloroform and 100ml of water, separating an organic phase, washing the organic phase for 2-3 times by using saturated saline, separating the organic phase, evaporating the solvent, recrystallizing the product by using 40ml of toluene to obtain 19.5g of a compound II with the yield of 94.7% and the purity of 97.5%;
In the second step, 20.6g (0.05 mol) of the product compound II obtained in the first step is dissolved in 200ml of methylene chloride as an organic solvent, 0.15mol of trifluoroacetic acid (50 wt% methanol) is gradually added dropwise to the solution, the reaction is stirred at room temperature, the progress of the reaction is monitored by HPLC, after the reaction is finished, a sodium bicarbonate solution is added to neutralize the reaction solution, the solvent is evaporated, 100ml of methylene chloride and 100ml of water are added, the organic phase is separated, the organic phase is washed 2 to 3 times with saturated saline solution, the crystallization is evaporated, and the product is recrystallized with 40ml of toluene to obtain 14.8g of compound III, the yield is 94.8%, and the purity is 97.6%.
Dissolving 23.2g (0.05 mol) of a compound I in 250ml of diethyl ether as an organic solvent under the protection of nitrogen, adding an ether solution (2.5 mol/L) of an alkali reagent n-butyllithium (0.1 mol), gradually adding a catalyst 0.05mol of triphenylphosphine, reacting for 30min at a low temperature of-20 to-10 ℃, then gradually heating to 20-30 ℃, continuing the reaction, monitoring the reaction by HPLC, detecting the end of the reaction, slowly dripping dry cyclohexane at the temperature of 0 ℃ for quenching the reaction, evaporating the solvent, adding 100ml of chloroform and 100ml of water, separating an organic phase, washing the organic phase for 2-3 times by using saturated saline, separating the organic phase, evaporating the solvent, recrystallizing the product by using 40ml of toluene to obtain 19.3g of a compound II, wherein the yield is 93.8% and the purity is 97.3%;
In the second step, 20.6g (0.05 mol) of the product compound II obtained in the first step is dissolved in 200ml of methylene chloride as an organic solvent, 0.15mol of trifluoroacetic acid (55 wt% methanol) is gradually added dropwise to the solution, the reaction is stirred at room temperature, the progress of the reaction is monitored by HPLC, after the reaction is finished, a sodium bicarbonate solution is added to neutralize the reaction solution, the solvent is evaporated, 100ml of methylene chloride and 100ml of water are added, the organic phase is separated, the organic phase is washed 2 to 3 times with saturated saline solution, the crystallization is evaporated, and the product is recrystallized with 40ml of toluene to obtain 14.7g of compound III, the yield is 94.2%, and the purity is 97.5%.
In the second step, 20.6g (0.05 mol) of the product compound II obtained in the first step is dissolved in 200ml of methylene chloride as an organic solvent, 0.15mol of trifluoroacetic acid (60 wt% methanol) is gradually added dropwise to the solution, the reaction is stirred at room temperature, the progress of the reaction is monitored by HPLC, after the reaction is finished, a sodium bicarbonate solution is added to neutralize the reaction solution, the solvent is evaporated, 100ml of methylene chloride and 100ml of water are added, the organic phase is separated, the organic phase is washed 2 to 3 times with saturated saline solution, the crystallization is evaporated, and the product is recrystallized with 40ml of toluene to obtain 14.8g of compound III, the yield is 94.8%, and the purity is 97.4%.
In the second step, 20.6g (0.05 mol) of the product compound II obtained in the first step is dissolved in 200ml of methylene chloride as an organic solvent, 0.15mol of trifluoroacetic acid (50 wt% methanol) is gradually added dropwise to the solution, the reaction is stirred at room temperature, the progress of the reaction is monitored by HPLC, after the reaction is finished, a sodium bicarbonate solution is added to neutralize the reaction solution, the solvent is evaporated, 100ml of methylene chloride and 100ml of water are added, the organic phase is separated, the organic phase is washed 2 to 3 times with saturated saline solution, the crystallization is evaporated, and the product is recrystallized with 40ml of toluene to obtain 14.6g of compound III, and the yield is 93.6% and the purity is 97.2%.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. Any reference sign in a claim should not be construed as limiting the claim concerned.
Furthermore, it should be understood that although the present disclosure describes embodiments, not every embodiment is provided with a separate embodiment, and that this description is provided for clarity only, and that the disclosure is not limited to the embodiments described in detail below, and that the embodiments described in the examples may be combined as appropriate to form other embodiments that will be apparent to those skilled in the art.
Claims (10)
1. The novel preparation method of oseltamivir is characterized by comprising the following steps of:
Dissolving a compound I in an organic solvent, adding an alkali reagent, gradually adding a catalyst triphenylphosphine, reacting for 30min at a low temperature of-20 to-10 ℃, then gradually heating to 20-30 ℃, continuing the reaction, monitoring the reaction by HPLC, detecting the termination of the reaction, and separating a product to obtain a compound II;
secondly, removing the protecting group of the product compound II obtained in the second step by adopting a deprotection agent to obtain a target compound III;
The specific reaction process flow is as follows:
。
2. The novel preparation method of oseltamivir according to claim 1, characterized in that: the solvent of the first reaction is anhydrous diethyl ether.
3. The novel preparation method of oseltamivir according to claim 1, characterized in that: the alkali reagent used in the first step is diethyl ether solution of n-butyllithium, and the concentration of the n-butyllithium is 2.5mol/L.
4. The novel preparation method of oseltamivir according to claim 1, characterized in that: the dosage of the alkali reagent in the first reaction is 1.5-2 eq of the compound I.
5. The novel preparation method of oseltamivir according to claim 1, characterized in that: the molar ratio of triphenylphosphine serving as a catalyst to the compound I in the first reaction step is 1:1.
6. The novel preparation method of oseltamivir according to claim 1, characterized in that: the deprotection agent used in the second reaction step is trifluoroacetic acid.
7. The novel oseltamivir preparation method according to claim 6, wherein: the trifluoroacetic acid is a solution in methanol solvent.
8. The novel preparation method of oseltamivir according to claim 1, characterized in that: the concentration of the deprotection agent sodium hydroxide/alcohol solution is 50-60 wt%.
9. The novel preparation method of oseltamivir according to claim 1, characterized in that: the molar ratio of the compound II to the deprotection agent in the second reaction step is 1:3.
10. The novel preparation method of oseltamivir according to claim 1, characterized in that: the organic solvent used in the second reaction step is dichloromethane.
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