公开(公告)号：US20210355070A1

公开(公告)日：2021-11-18

申请号：US17384747

申请日：2021-07-24

Applicant: Fudan University

Inventor： Fener CHEN ,  Meifen JIANG ,  Minjie LIU ,  Dang CHENG ,  Chao YU ,  Huashan HUANG

IPC: C07C67/31 ,  B01J19/00

Abstract: This disclosure relates to organic synthesis, and more particularly to a method for preparing 3-chloro-4-oxopentyl acetate using a fully continuous-flow micro-reaction system. In this method, chlorine and an acetylbutyrolactone-containing liquid are simultaneously transported to a first micro-channel reactor for continuous chlorination to obtain α-acetyl-α-chloro-γ-butyrolactone. The reaction mixture is simultaneously transported to a micro-mixer and a second micro-channel reactor together with a mixed solution of glacial acetic acid, hydrochloric acid and water, and the continuous acylation is carried out to obtain 3-chloro-4-oxopentyl acetate. After quenched with a quenching agent, the reaction mixture was subjected to extraction and separation to obtain the 3-chloro-4-oxopentyl acetate.

公开(公告)号：US20200055811A1

公开(公告)日：2020-02-20

申请号：US16288031

申请日：2019-02-27

Applicant: FUDAN UNIVERSITY

Inventor： Fener CHEN ,  Lingdong WANG ,  Ge MENG ,  Zedu HUANG ,  Dang CHENG ,  Haihui PENG ,  Guanfeng LIANG

IPC: C07C227/18 ,  C07C201/08 ,  C07C227/06 ,  C07C227/16

Abstract: The invention relates to the chemical synthesis of pharmaceutical API, and specifically to a method of synthesizing diclofenac sodium, which is a kind of nonsteroidal anti-inflammatory drug for relieving pain. The method includes: nitrating phenylacetate to prepare o-nitrophenylacetate (2); hydrogenating o-nitrophenylacetate (2) to prepare o-aminophenylacetate (3); amidating an amino group of o-aminophenylacetate (3) to obtain 2-(2-benzoylaminophenyl) acetate (4); 2-(2-benzoylaminophenyl) acetate (4) reacting with thionyl chloride to prepare a chloroimine intermediate, and then condensing the intermediate of chloroimine with 2,6-dichlorophenol using an inorganic base to prepare (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5); subjecting (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5) to Chapman rearrangement to afford methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6); and hydrolyzing methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6) to provide the target compound as of diclofenac sodium API. The overall yield is up to 67% based on methyl phenylacetate.

公开(公告)号：US20180340196A1

公开(公告)日：2018-11-29

申请号：US15871039

申请日：2018-01-14

Applicant: FUDAN UNIVERSITY

Inventor： Fener CHEN ,  Zedu HUANG ,  Ge MENG ,  Minjie LIU ,  Zhining LI ,  Zexu WANG ,  Haihui PENG ,  Fangjun XIONG ,  Yan WU ,  Yuan TAO

IPC: C12P7/62 ,  C07C69/732 ,  C07C67/28 ,  C12N9/04

CPC classification number: C12P7/62 ,  C07C67/28 ,  C07C69/732 ,  C12N9/0006 ,  C12Y101/0108 ,  G01N30/7206 ,  G01N30/88 ,  G01N2030/025

Abstract: The present disclosure relates to the technical field of biochemical engineering and particularly discloses a preparation method for (R)-3-hydroxyl-5-hexenoate. In the method of the present disclosure, the (R)-3-hydroxyl-5-hexenoate is prepared by catalytic reduction of 3-carbonyl-5-hexenoate by ketoreductase with 3-carbonyl-5-hexenoate as the substrate. The amino acid sequence of ketoreductase is shown in SEQ ID NO.1. In the present disclosure, the (R)-3-hydroxyl-5-hexenoate having a very high chiral purity is obtained by asymmetric reduction by ketoreductase as the biocatalyst. The present disclosure has the advantages of easy operation, mild reaction conditions, high reaction yield and good practical industrial application value.

公开(公告)号：US20230192595A1

公开(公告)日：2023-06-22

申请号：US18172865

申请日：2023-02-22

Applicant: Fudan University

Inventor： Fener CHEN ,  Dang CHENG ,  Lulu WANG ,  Ge MENG ,  Yingtang NING

IPC: C07C227/18 ,  C07C227/40

CPC classification number: C07C227/18 ,  C07C227/40

Abstract: This application relates to pharmaceutical engineering, and more particularly to a continuous-flow preparation method of diclofenac sodium. The continuous-flow preparation method includes: subjecting aniline and chloroacetic acid to amidation to obtain 2-chloro-N-phenylacetamide (3); subjecting 2-chloro-N-phenylacetamide (3) and 2,6-dichlorophenol to continuous condensation to obtain N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (5); subjecting N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (5) and thionyl chloride to chlorination to obtain N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (6); subjecting N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (6) to Friedel-Crafts alkylation in the presence of aluminum chloride to obtain 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indo1-2-one (7); and subjecting 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one (7) to hydrolysis to obtain the diclofenac sodium.

公开(公告)号：US20230183196A1

公开(公告)日：2023-06-15

申请号：US18166478

申请日：2023-02-09

Applicant: Fudan University

Inventor： Fener CHEN ,  Meifen JIANG ,  Minjie LIU ,  Yingqi XIA ,  Weijian LI

IPC: C07D279/06

CPC classification number: C07D279/06

Abstract: to enter a second continuous filtration and reaction device for filtration to collect a filter cake; and subjecting the filter cake to reaction with organic hydrochloric acid solution followed by filtration and drying to obtain vitamin B1.

公开(公告)号：US20230127147A1

公开(公告)日：2023-04-27

申请号：US18068151

申请日：2022-12-19

Applicant: Fudan University

Inventor： Fener CHEN ,  Minjie LIU ,  Meifen JIANG ,  Yingqi XIA ,  Huashan HUANG

IPC: C07C315/02 ,  C07C315/06

Abstract: A continuous-flow preparation method of diol sulfone using a two-stage micro-reaction system. The system includes a first micro-mixer, a first micro-channel reactor, a second micro-mixer, and a second micro-channel reactor communicated in sequence. The method includes: feeding hydrogen peroxide, a catalyst and a diol thioether solution simultaneously to the first micro-mixer followed by mixing; feeding the reaction mixture to the first micro-channel reactor for continuous oxidation; and feeding the reaction mixture and water simultaneously to the second micro-mixer and the second micro-channel reactor for continuous quenching and crystallization to obtain diol sulfone.

公开(公告)号：US20220281840A1

公开(公告)日：2022-09-08

申请号：US17740275

申请日：2022-05-09

Applicant: Fudan University

Inventor： Fener CHEN ,  Liangchuan LAI ,  Baijun YE ,  Meifen JIANG

IPC: C07D401/12 ,  B01J4/00 ,  B01J8/02

Abstract: Disclosed is a method of continuously preparing N,N-Bis(2,2,6,6-tetramethyl-4-piperidyl)-1,6-hexamethylenediamine, which relates to chemical engineering. The Pt/C catalyst and the quartz sand are mixed uniformly and loaded to the continuous-flow fixed-bed reactor. Then, hydrogen gas and a substrate solution containing 2,2,6,6-tetramethyl-4-piperidinone and 1,6-hexanediamine are simultaneously fed to the micro-mixer and the continuous-flow fixed-bed reactor in sequence to undergo a continuous catalytic reductive amination to obtain the N,N-Bis(2,2,6,6-tetramethyl-4-piperidyl)-1,6-hexamethylenediamine.

公开(公告)号：US20220089524A1

公开(公告)日：2022-03-24

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

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：US20210394148A1

公开(公告)日：2021-12-23

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

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：US20210394141A1

公开(公告)日：2021-12-23

申请号：US17467377

申请日：2021-09-06

Applicant: Fudan University

Inventor： Fener CHEN ,  Dang CHENG ,  Minjie LIU ,  Huashan HUANG ,  Meifen JIANG ,  Jiaqi WANG

IPC: B01F15/00 ,  B01F13/00

Abstract: A multi-layered micro-channel mixer includes a base plate and a cover plate. Two inlet fluid reservoirs, two inlet channels, two groups of fluid distribution channel networks, two groups of process fluid channels, an impinging stream mixing chamber, a fluid mixing intensification channel and an outlet buffer reservoir are provided on the base plate. Two fluids are fed into the two inlet fluid reservoirs, respectively. The fluids then flow into the process fluid channels via the inlet channels and the multi-stage fluid distribution channel networks, respectively. Then the two fluid streams ejected from the opposing process fluid channels impinges upon each other in the impinging stream mixing chamber. The mixed fluid is subjected to vortex or secondary flow generated by the baffles or the internals in the impinging stream mixing chamber and fluid mixing intensification channel, and finally the mixed fluid is discharged through the outlet buffer reservoir.