CN113896676B - Method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan - Google Patents

Method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan Download PDF

Info

Publication number
CN113896676B
CN113896676B CN202111368984.5A CN202111368984A CN113896676B CN 113896676 B CN113896676 B CN 113896676B CN 202111368984 A CN202111368984 A CN 202111368984A CN 113896676 B CN113896676 B CN 113896676B
Authority
CN
China
Prior art keywords
aminomethyl
furan
bis
catalyst
aminomethylpiperidine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202111368984.5A
Other languages
Chinese (zh)
Other versions
CN113896676A (en
Inventor
王延吉
张树兴
丁晓墅
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hebei University of Technology
Original Assignee
Hebei University of Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hebei University of Technology filed Critical Hebei University of Technology
Priority to CN202111368984.5A priority Critical patent/CN113896676B/en
Publication of CN113896676A publication Critical patent/CN113896676A/en
Application granted granted Critical
Publication of CN113896676B publication Critical patent/CN113896676B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
    • B01J23/46—Ruthenium, rhodium, osmium or iridium
    • B01J23/464—Rhodium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/54—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals combined with metals, oxides or hydroxides provided for in groups B01J23/02 - B01J23/36
    • B01J23/56—Platinum group metals
    • B01J23/63—Platinum group metals with rare earths or actinides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J29/00—Catalysts comprising molecular sieves
    • B01J29/04—Catalysts comprising molecular sieves having base-exchange properties, e.g. crystalline zeolites
    • B01J29/06—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof
    • B01J29/40—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof of the pentasil type, e.g. types ZSM-5, ZSM-8 or ZSM-11, as exemplified by patent documents US3702886, GB1334243 and US3709979, respectively
    • B01J29/42—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof of the pentasil type, e.g. types ZSM-5, ZSM-8 or ZSM-11, as exemplified by patent documents US3702886, GB1334243 and US3709979, respectively containing iron group metals, noble metals or copper
    • B01J29/44—Noble metals

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Hydrogenated Pyridines (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The invention relates to a method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-di (aminomethyl) furan. The method comprises the following steps: 2, 5-bis (aminomethyl) furan, a catalyst and an organic solvent are added into a reactor under the condition of H of 1-8 MPa 2 Reacting for 0.5-8 h at 120-200 ℃ under pressure to obtain a product 2-aminomethyl piperidine; the catalyst is a supported metal catalyst, and the active metal is Ru, rh or Pt; the catalyst carrier is gamma-Al 2 O 3 、TiO 2 、SiO 2 、ZrO 2 、CeO 2 ZSM-5 or activated carbon. The invention has mild reaction condition, product selectivity of more than 80 percent and simple preparation process of the metal catalyst.

Description

Method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan
Technical Field
The invention relates to a method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-di (aminomethyl) furan.
Background
2-amino methyl piperidine is an important organic compound and an intermediate for synthesizing pesticides and medicines. For the synthesis of pharmaceutically active ingredients, 2-aminomethylpiperidine is an essential building block. One of these pharmaceutically active ingredients is flecainide (flecainide).
2-Aminomethylpiperidine is usually prepared by hydrogenation of 2-cyanopyridine. However, the process used is a two-step process and the overall yield is only around 20%. The second step also needs to be carried out in acetic acid or other mineral acids. The use of 2-aminomethylpyridines for the preparation of 2-aminomethylpiperidines also has the above-mentioned problems.
Disclosure of Invention
The invention aims to provide a method for preparing 2-aminomethyl piperidine by using biomass derivative 2, 5-di (aminomethyl) furan as a raw material through selective hydrogenolysis aiming at the defects of the current 2-aminomethyl piperidine synthesis technology. The method uses biomass derived 2, 5-bis (aminomethyl) furan as a raw material, metals Ru, rh and Pt in the catalyst are metal components, and gamma-Al 2 O 3 、TiO 2 、SiO 2 、ZrO 2 、CeO 2 ZSM-5 or active carbon as carrier. 2-aminomethyl piperidine is prepared by the selective hydrogenolysis of 2, 5-di (aminomethyl) furan under mild conditions. The invention has mild reaction condition, product selectivity of over 80 percent and goldThe preparation process of the catalyst is simple.
The technical scheme of the invention is as follows:
a process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to produce 2-aminomethylpiperidine which comprises the steps of: adding 2, 5-di (aminomethyl) furan, a catalyst and an organic solvent into a reactor, and reacting at 1-8 MPa of H 2 Reacting for 0.5-8 h under the pressure and at the temperature of 120-200 ℃ to obtain a product 2-aminomethyl piperidine;
wherein, 2-15 mL of solvent is added into every 1mmol of 2, 5-bis (aminomethyl) furan in material proportion; adding 0.05-0.5 g of metal catalyst into 1mmol of 2, 5-bis (aminomethyl) furan;
the catalyst is a supported metal catalyst, and comprises active metal and a carrier; the metal loading is 2wt% -10 wt%;
the active metal is Ru, rh or Pt;
the catalyst carrier is gamma-Al 2 O 3 、TiO 2 、SiO 2 、ZrO 2 、CeO 2 ZSM-5 or activated carbon;
the organic solvent is tetrahydrofuran, 1,4 dioxane or n-decane;
the reactor is a high-pressure reactor;
the material proportion is preferably that 5-10 mL of solvent is added into every 1mmol of 2, 5-bis (aminomethyl) furan; adding 0.1-0.5 g of metal catalyst into every 1mmol of 2, 5-bis (aminomethyl) furan;
the preparation process of the catalyst comprises the following steps: soaking the water solution of the active metal component precursor and the carrier in the same volume according to the required proportion, standing for 10-15h, drying for 10-12 h at 100-120 ℃, calcining for 2-5 h at 300-550 ℃ by using a muffle furnace, and finally reducing for 1-3 h at 200-500 ℃ by using hydrogen;
the active metal component precursor is hydrochloride, nitrate or acetate;
the preferable hydrogen pressure is 3-8 MPa; the reaction temperature is preferably 130-180 ℃; the reaction time is preferably 1 to 4 hours.
The beneficial effects of the invention are as follows:
(1) The method realizes the selective hydrogenolysis of 2, 5-di (aminomethyl) furan to prepare the 2-aminomethyl piperidine for the first time. The metal catalyst has good catalytic performance, and the product selectivity can reach more than 80 percent at most.
(2) The reaction condition is mild, and the preparation process of the metal catalyst is simple.
(3) After the reaction is finished, the reaction liquid can be subjected to centrifugal separation, and the metal catalyst is deposited at the bottom and can be recycled, so that the method has a good application prospect.
Detailed Description
The reaction formula for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan according to the present invention is as follows:
Figure BDA0003346561160000021
the invention relates to a preparation method of 2, 5-di (aminomethyl) furan by reductive amination of 5-hydroxymethylfurfural which is a biomass platform compound.
The supported metal catalyst is a known material, and the composition of the catalyst comprises an active metal and a carrier. The following are Rh/gamma-Al in which the loading is 2wt% 2 O 3 But not limited thereto:
first, the gamma-Al of the carrier is measured 2 O 3 Saturated water absorption amount of (d): accurately weighing 2.0g of the carrier on a watch glass, dropwise adding pure water until the carrier is completely soaked and slightly flows, and recording the volume of the used pure water, namely the saturated water absorption capacity of the carrier.
Step two, preparing a supported metal catalyst by an impregnation method: accurately weighing 2.0g of carrier in a crucible. Accurately weighing 0.104g of RhCl 3 ·xH 2 O in a beaker, the saturated water absorption of the support measured in the first step was added. The rhodium solution was added dropwise to the support until the support was completely wetted and slightly fluid. After standing for 12 hours, the mixture was dried overnight at 110 ℃ using a drying oven. Finally, the catalyst is roasted by a muffle furnace for 3 hours at 300 ℃.
Step three, catalyst reduction: before the use of the medical instrument, the patient can be put into practice,the catalyst was reduced using a tubular resistance furnace at 300 ℃ and a flow rate H of 100mL/min 2 The reduction was carried out for 1h, and the theoretical loading of the finally obtained catalyst, metal Rh, was 2wt%.
Example 1
1mmol of 2, 5-bis (aminomethyl) furan, 0.1g of Rh/gamma-Al with a loading of 2wt% 2 O 3 Adding a catalyst and 5mL of tetrahydrofuran into a 25mL high-pressure reaction kettle, replacing air in the reaction kettle with nitrogen for 4 times, replacing the nitrogen in the reaction kettle with hydrogen for 4 times, and filling hydrogen to 5MPa. After warming to 150 ℃, stirring was started. The reaction was completed for 8h and cooled to room temperature. Centrifuging to separate supernatant, precipitating catalyst at the bottom, filtering supernatant, and directly analyzing on gas chromatography. By plotting a working curve by an external standard method, it was confirmed that the conversion of 2, 5-bis (aminomethyl) furan was 100%, the yield of 2-aminomethylpiperidine was 80.2%, and the remaining product was 2, 5-bis (aminomethyl) tetrahydrofuran and the like.
Example 2
The procedure is otherwise as in example 1, except that Rh/TiO is used as the catalyst 2 As a result of the reaction, the conversion of 2, 5-bis (aminomethyl) furan was 100%, and the yield of 2-aminomethylpiperidine was 64.6%.
Example 3
The procedure of example 1 was repeated except that Rh/ZSM-5 was used as the catalyst, and the reaction resulted in 100% conversion of 2, 5-bis (aminomethyl) furan and 54.0% yield of 2-aminomethylpiperidine.
Example 4
The other procedure was the same as in example 1, except that Pt/ZrO was added as the catalyst 2 As a result of the reaction, the conversion of 2, 5-bis (aminomethyl) furan was 86.3%, and the yield of 2-aminomethylpiperidine was 54.0%.
Example 5
The other procedure was the same as in example 1 except that Pt/CeO was used as the catalyst 2 As a result, the conversion of 2, 5-bis (aminomethyl) furan was 90.2%, and the yield of 2-aminomethylpiperidine was 67.0%.
Example 6
The other steps were the same as in example 1 except that the reaction pressure was 6MPa, the conversion of 2, 5-bis (aminomethyl) furan was 100% and the yield of 2-aminomethylpiperidine was 84.7%.
Example 7
The other steps were the same as in example 1 except that the catalyst loading was 5% by weight, and the reaction resulted in 100% conversion of 2, 5-bis (aminomethyl) furan and 75.3% yield of 2-aminomethylpiperidine.
Example 8
The other steps were the same as in example 1 except that the catalyst was reused 5 times, and the reaction resulted in 100% conversion of 2, 5-bis (aminomethyl) furan and 76.5% yield of 2-aminomethylpiperidine.
The object of the present invention was therefore to find a practical, economical and green process which makes it possible to prepare 2-aminomethylpiperidine on an industrial scale in a simple manner. Surprisingly, it has been found that 2-aminomethylpiperidines can be prepared by selective hydrogenolysis starting from biobased-derived 2, 5-bis (aminomethyl) furan.
The above description is only a part of specific examples of the present invention, but the scope of the present invention is not limited thereto, and the present invention is not limited by the order of the examples, and any person skilled in the art of the present invention can easily change or replace the technical scope of the present invention within the technical scope reported by the present invention, and shall be covered by the scope of the present invention. Therefore, the protection scope of the present invention is not limited to the above embodiments, and the protection scope of the claims should be subject to.
The invention is not the best known technology.

Claims (7)

1. A process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to produce 2-aminomethylpiperidine, characterized in that the process comprises the steps of: adding 2, 5-bis (aminomethyl) furan, a catalyst and an organic solvent into a reactor, and reacting at 1-8MPa of H 2 Reacting for 0.5 to 8 hours at the temperature of 120 to 200 ℃ under pressure to obtain a product 2-aminomethyl piperidine;
wherein, 2 to 15mL of solvent is added into every 1mmol of 2, 5-bis (aminomethyl) furan; adding 0.05 to 0.5g of metal catalyst into every 1mmol of 2, 5-bis (aminomethyl) furan;
the catalyst is a supported metal catalyst, and comprises active metal and a carrier; the metal loading is 2-10 wt%;
the active metal is Ru, rh or Pt;
the catalyst carrier is gamma-Al 2 O 3 、TiO 2 、SiO 2 、ZrO 2 、CeO 2 ZSM-5 or activated carbon.
2. The process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to 2-aminomethylpiperidine as in claim 1 wherein the organic solvent is tetrahydrofuran, 1, 4-dioxane or n-decane.
3. The process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to 2-aminomethylpiperidine as in claim 1 wherein the reactor is a high pressure reactor.
4. The process for preparing 2-aminomethylpiperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan according to claim 1, wherein the feed ratio is preferably 5 to 10mL of solvent per 1mmol of 2, 5-bis (aminomethyl) furan; 0.1 to 0.5g of a metal catalyst was added to 1mmol of 2, 5-bis (aminomethyl) furan.
5. The process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to 2-aminomethylpiperidine according to claim 1 wherein the catalyst is prepared by: soaking the aqueous solution of the active metal component precursor and the carrier in the required proportion in the same volume, standing for 10 to 15h, drying for 10 to 12h at 100 to 120 ℃, calcining for 2 to 5h at 300 to 550 ℃ by using a muffle furnace, and finally reducing for 1 to 3h at 200 to 500 ℃ by using hydrogen.
6. The process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to produce 2-aminomethylpiperidine as in claim 5 wherein the precursor active metal component is a hydrochloride, nitrate or acetate salt.
7. The process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to 2-aminomethylpiperidine as in claim 5 wherein the hydrogen pressure is 3 to 8MPa; the reaction temperature is 130 to 180 ℃; the reaction time is 1 to 4 hours.
CN202111368984.5A 2021-11-10 2021-11-10 Method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan Active CN113896676B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111368984.5A CN113896676B (en) 2021-11-10 2021-11-10 Method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111368984.5A CN113896676B (en) 2021-11-10 2021-11-10 Method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan

Publications (2)

Publication Number Publication Date
CN113896676A CN113896676A (en) 2022-01-07
CN113896676B true CN113896676B (en) 2023-02-10

Family

ID=79194668

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111368984.5A Active CN113896676B (en) 2021-11-10 2021-11-10 Method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan

Country Status (1)

Country Link
CN (1) CN113896676B (en)

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0670012B2 (en) * 1985-04-30 1994-09-07 広栄化学工業株式会社 Process for producing 2- or 3-aminomethylpiperidine
DE4132808A1 (en) * 1991-10-02 1993-04-08 Hoechst Ag PROCESS FOR THE PREPARATION OF 2-AMINOMETHYLPIPERIDINE
CN102093283A (en) * 2009-12-10 2011-06-15 中国科学院大连化学物理研究所 Method for preparing piperidine and piperidine derivative
CN105251491B (en) * 2015-11-09 2018-03-27 中国科学院化学研究所 A kind of 5 hydroxymethylfurfural selectivity hydrogenolysis prepares catalyst of 2,5 dimethyl furans and preparation method thereof
CN110290870B (en) * 2017-02-13 2022-08-23 株式会社大赛璐 Catalyst for reduction reaction of 3, 4-dihydroxytetrahydrofuran and method for producing reduced product thereof
CN107282041B (en) * 2017-06-01 2019-12-13 浙江理工大学 Preparation method of catalyst for producing DMF (dimethyl formamide) by transferring and hydrogenating HMF (dimethyl formamide)
CN110655495B (en) * 2019-11-07 2023-04-07 中国科学院兰州化学物理研究所 Method for synthesizing 1-methylpiperidine by supported metal catalysis
CN112958133B (en) * 2021-02-09 2022-05-03 浙江理工大学 Palladium carbon catalyst and method for preparing N-ethyl-2, 6-methylpiperidine by using same

Also Published As

Publication number Publication date
CN113896676A (en) 2022-01-07

Similar Documents

Publication Publication Date Title
CN111116381B (en) Method for preparing 1, 3-cyclohexyldimethylamine by m-xylylenediamine hydrogenation
CN111574483B (en) Preparation method of 2, 5-furandimethanol
JP6040597B2 (en) Method for producing 1,4-butanediol
CN1149192C (en) Process for preparing protected 4-aminomethyl-pyrrolidin-3-one
US20140228596A1 (en) Process for preparing 1,6-hexanediol
CN114308035A (en) Hydrogenation catalyst for 1, 4-cyclohexanedicarboxylic acid, preparation method and application thereof
CN1138595C (en) Catalysts supports, supported catalysts and process for the manufacture of 1,2-epoxibutane
JP2015519354A (en) Process for producing mono-N-alkyl-piperazine
WO2018085957A1 (en) Process for production of aromatic compounds comprising at least two amine functions
CN113877630B (en) Catalyst for preparing bis [ (3-dimethylamino) propyl ] amine and application thereof
JP2543929B2 (en) Method for hydrogenating citric acid and substituted citric acid to 3-substituted tetrahydrofuran, 3- and 4-substituted butyrolactone and mixtures thereof
CN111499603B (en) Method for preparing furfuryl alcohol by catalytic conversion of furfural
CN113896676B (en) Method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan
CS48692A3 (en) Supported catalyst based on a noble metal, a process for preparing saidcatalyst and a process for preparing a mixture of cyclohexylamine anddicyclohexylamine by utilizing said catalyst
CN113354602B (en) Method for preparing 2-methyltetrahydrofuran from furfural through one-step hydrogenation
CN112079798A (en) Method for preparing 2, 5-dicyano tetrahydrofuran by selective hydrogenation of 2, 5-dicyano furan
NO324896B1 (en) Process for the preparation of racemic amines
JP2002536427A (en) Racemization of optically active amines
JP2004517135A (en) Method for producing saturated organic compound
JP3726504B2 (en) Catalyst regeneration method and hydrogenation method using regenerated catalyst
CN1173902C (en) Racemization of optically active amines
JP2002226437A (en) Method for racemizing optically active amine
CN108620103B (en) Catalyst for preparing (S) -3-hydroxytetrahydrofuran and preparation and use methods thereof
CN114805098B (en) Method for synthesizing 5-amino-1-amyl alcohol by using furfural as initial raw material
US20040138266A1 (en) Method for producing-2[-5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant