公开(公告)号：US10316012B1

公开(公告)日：2019-06-11

申请号：US16246531

申请日：2019-01-13

Applicant: FUDAN UNIVERSITY

Inventor： Fener Chen ,  Haihui Peng ,  Sha Hu ,  Ge Meng ,  Yan Wu ,  Dang Cheng ,  Zedu Huang ,  Guanfeng Liang

IPC: C07D307/93

Abstract: Disclosed is a method of synthesizing a series of compounds with the structure of (1S, 5R)-lactone. In the method, under the catalysis of a chiral phosphonic acid, substituted bicyclo[3.2.0]-hept-2-en-6-one (II) as a substrate is reacted with hydrogen peroxide for enantioselective Baeyer-Villiger oxidation to produce a chiral lactone (I). This method involves mild reaction conditions, simple operation, quantitatively recyclable catalyst and high reaction selectivity and stereoselectivity, which is suitable for industrial production.

公开(公告)号：US12281348B2

公开(公告)日：2025-04-22

申请号：US17516894

申请日：2021-11-02

Applicant: Fudan University

Inventor： Fener Chen ,  Dang Cheng ,  Zedu Huang ,  Minjie Liu ,  Huashan Huang ,  Meifen Jiang ,  Lulu Wang

IPC: C12M1/00 ,  C12M1/02 ,  C12M1/34 ,  C12M1/36 ,  C12P7/625

Abstract: This application relates to organic synthesis, and more particularly to a method for the continuous flow synthesis of (R)-4-halo-3-hydroxy-butyrate using a micro-reaction system. This application performs an enzymatic asymmetric reduction of a substrate solution containing halogenated acetoacetate and a biocatalyst solution in the micro-reaction system composed of a micro-mixer, a micro-channel reactor, and a pH regulator to obtain the (R)-4-halo-3-hydroxy-butyrate. Compared to the prior art, the reaction time of the method is only a few minutes, the yield of the product (R)-4-halo-3-hydroxy-butyrate is greater than 95%, the reaction process is continuous, the degree of automation is high, the efficiency is high, and the process is simple to operate and easy to be used in industrialized production.

公开(公告)号：US11913055B2

公开(公告)日：2024-02-27

申请号：US17504858

申请日：2021-10-19

Applicant: Fudan University

Inventor： Fener Chen ,  Dang Cheng ,  Zedu Huang ,  Chen Hu ,  Meifen Jiang ,  Minjie Liu ,  Huashan Huang

IPC: C12P7/42 ,  C12P7/62 ,  C12N9/04 ,  C12M3/06 ,  C12N11/084 ,  C12N11/089 ,  C12M1/40 ,  C12M1/00

CPC classification number: C12P7/62 ,  C12M21/18 ,  C12M23/16 ,  C12M29/00 ,  C12N11/084 ,  C12N11/089 ,  C12Y101/0108 ,  C12Y101/01184

Abstract: Disclosed herein relates to biopharmaceuticals, and more particularly to a continuous flow method for preparing (R)-3-hydroxy-5-hexenoate. Carbonyl reductase and isopropanol dehydrogenase are co-immobilized onto an inert solid medium simultaneously to prepare a carbonyl reductase/isopropanol dehydrogenase co-immobilized catalyst, which is then filled into a microchannel reactor of the micro reaction system. A solution containing substrate 3-carbonyl-5-hexenoate is subsequently pumped into the microchannel reactor to perform an asymmetric carbonyl reduction reaction to obtain (R)-3-hydroxy-5-hexenoate.

公开(公告)号：US11905229B2

公开(公告)日：2024-02-20

申请号：US18172414

申请日：2023-02-22

Applicant: Fudan University

Inventor： Fener Chen ,  Dang Cheng ,  Lulu Wang ,  Ge Meng ,  Yingtang Ning ,  Zedu Huang

IPC: C07C227/18 ,  B01J21/02

CPC classification number: C07C227/18 ,  B01J21/02

Abstract: A method of synthesizing diclofenac sodium, including: subjecting aniline and chloroacetic acid to amidation to obtain 2-chloro-N-phenylacetamide; subjecting 2-chloro-N-phenylacetamide and 2,6-dichlorophenol to condensation reaction to obtain 2-(2,6-dichlorophenoxy)-N-phenylacetamide; subjecting 2-(2,6-dichlorophenoxy)-N-phenylacetamide to Smiles rearrangement in the presence of an inorganic base to obtain N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide; subjecting N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide and thionyl chloride to chlorination to obtain N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide; subjecting N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide to Friedel-Crafts alkylation in the presence of a Lewis acid catalyst to obtain 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one; and subjecting 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one to hydrolysis in the presence of an inorganic base to obtain diclofenac sodium.

公开(公告)号：US11827581B2

公开(公告)日：2023-11-28

申请号：US17741112

申请日：2022-05-10

Applicant: Fudan University

Inventor： Fener Chen ,  Minjie Liu ,  Meifen Jiang ,  Dang Cheng ,  Chao Yu ,  Huashan Huang

IPC: C07C227/12 ,  C07C227/08 ,  B01J19/00

CPC classification number: C07C227/12 ,  B01J19/0093 ,  C07C227/08 ,  B01J2219/0086 ,  B01J2219/00867 ,  B01J2219/00889 ,  C07C227/08 ,  C07C229/22

Abstract: A full continuous-flow preparation method of L-carnitine, including: mixing chlorine gas and a diketene solution via a first micromixer followed by transportation to a first microchannel reactor for continuous chlorination and esterification reaction to obtain 4-chloroacetoacetate; feeding the 4-chloroacetoacetate and a reductase to a second micromixer and a second microchannel reactor in sequence for continuous catalytic reaction to obtain (R)-4-chloro-3-hydroxybutyrate; simultaneously transporting the (R)-4-chloro-3-hydroxybutyrate and a trimethylamine solution to a third micromixer and a third microchannel reactor for continuous substitution and hydrolysis reaction; and subjecting the reaction mixture to desalination and concentration to obtain the L-carnitine.

公开(公告)号：US11708321B2

公开(公告)日：2023-07-25

申请号：US17103520

申请日：2020-11-24

Applicant: Fudan University

Inventor： Fener Chen ,  Dang Cheng ,  Meifen Jiang ,  Minjie Liu ,  Huashan Huang ,  Lulu Wang

IPC: C07C253/20 ,  B01J19/00 ,  C07C255/25

CPC classification number: C07C253/20 ,  B01J19/0093 ,  B01J2219/00797 ,  B01J2219/00867 ,  B01J2219/00891 ,  B01J2219/00997 ,  C07C255/25

Abstract: A method for preparing (dimethylaminomethylene) malononitrile by using a micro reaction system. Cyanoacetamide, N,N-dimethylformamide and a catalyst are mixed to obtain a mixture, and the mixture and phosphorus oxychloride are simultaneously pumped into the micro reaction system that includes a micromixer and a microchannel reactor connected in series for continuous dehydration condensation. After adjusted to a target pH, the crude product is subjected to continuous liquid-liquid extraction with an organic solvent in a centrifugal extraction unit comprising a plurality of annular centrifugal extractors connected in series. The organic phase is collected to obtain the target product (dimethyl aminomethylene) malononitrile.

公开(公告)号：US11554356B2

公开(公告)日：2023-01-17

申请号：US17467091

申请日：2021-09-03

Applicant: Fudan University

Inventor： Fener Chen ,  Meifen Jiang ,  Minjie Liu ,  Huashan Huang ,  Dang Cheng

IPC: B01J19/00 ,  B01J25/02 ,  C07D239/42

Abstract: A full continuous flow preparation method of 2-methyl-4-amino-5-aminomethylpyrimidine. A mixed solution of cyanoacetamide, N,N-dimethylformamide and a catalyst is mixed with phosphorus oxychloride in a first micro-mixer, and then the reaction mixture undergoes continuous flow reaction in a microchannel reactor to obtain (dimethylaminomethylene) malononitrile. The reaction mixture is subjected to continuous quenching, extraction and separation, and the organic phase is concentrated, mixed with a methanol solution, and then reacted with an organic base to obtain 2-methyl-4-amino-5-cyanopyrimidine. After the mixed liquid is continuously filtered, the filter cake is dissolved in methanol, mixed with hydrogen in a second micro-mixer, and then transported to a fixed-bed reactor for hydrogenation reaction. The products are concentrated, dried and purified to obtain the desired 2-methyl-4-amino-5-aminomethylpyrimidine.

公开(公告)号：US11554354B2

公开(公告)日：2023-01-17

申请号：US17467041

申请日：2021-09-03

Applicant: Fudan University

Inventor： Fener Chen ,  Meifen Jiang ,  Dang Cheng ,  Minjie Liu ,  Huashan Huang

IPC: B01J8/00 ,  B01J8/02 ,  B01J8/06 ,  B01J19/00 ,  B01J23/755 ,  B01J25/02 ,  C07D239/42

Abstract: A micro-reaction system and a method for preparing 2-methyl-4-amino-5-aminomethyl pyrimidine. A Raney nickel catalyst is modified with formalin, and the modified Raney nickel catalyst is filled into a micro-channel reactor of the micro-reaction system. A substrate solution containing 2-methyl-4-amino-5-cyanopyrimidine and a base and hydrogen are transported to the micro-mixer and the micro-channel reactor in sequence for continuous catalytic hydrogenation to obtain 2-methyl-4-amino-5-aminomethyl pyrimidine.

公开(公告)号：US10214506B2

公开(公告)日：2019-02-26

申请号：US15871049

申请日：2018-01-14

Applicant: FUDAN UNIVERSITY

Inventor： Fener Chen ,  Guanxin Huang ,  Ge Meng ,  Minjie Liu ,  Yan Wu ,  Dang Cheng ,  Zedu Huang ,  Haihui Peng ,  Fangjun Xiong

IPC: C07D319/06 ,  C07B47/00 ,  C07B41/12

Abstract: The present disclosure belongs to the technical field of organic synthesis and particularly relates to a preparation method for 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate. The 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate is a key chiral intermediate for preparation of statin antilipemic agents. In the present disclosure, the 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate is obtained by bromination and cyclization of 3-((substituted oxycarbonyl)oxy)-5-hexenoate as raw material with hypochlorite and bromide in an organic solvent in the presence of CO2. The method of the present disclosure has the advantages of readily available raw material, mild reaction conditions, easy operation, low cost, excellent atomic economy and less by-products, and is applicable to industrial production.