公开(公告)号：US20220033863A1

公开(公告)日：2022-02-03

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: C12P7/62 ,  C12N11/084 ,  C12M1/40 ,  C12M3/06 ,  C12M1/00 ,  C12N11/089

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：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：US20220056489A1

公开(公告)日：2022-02-24

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: C12P7/62 ,  C12M1/02 ,  C12M1/34 ,  C12M1/36 ,  C12M1/00

Abstract: A method for the continuous flow synthesis of (R)-4-halo-3-hydroxy-butyrate using a micro-reaction system. The micro-reaction system includes a micro-mixer, a certain number of micro-reaction units that are successively connected in series, a pH regulating system and a back pressure valve. The micro-reaction unit is composed of a micro-channel reactor and a pH regulator that are sequentially connected with each other. A substrate solution containing halogenated acetoacetate and a biocatalyst solution are simultaneously pumped into the micro-reaction system to enable continuous flow biocatalytic asymmetric reduction reaction of the halogenated acetoacetate to obtain the target product (R)-4-halo-3-hydroxy-butyrate.

公开(公告)号：US20210394150A1

公开(公告)日：2021-12-23

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 ,  C07D239/42 ,  B01J25/02

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：US20220267253A1

公开(公告)日：2022-08-25

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 ,  B01J19/00

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：US20210394149A1

公开(公告)日：2021-12-23

申请号：US17467060

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

Abstract: Disclosed herein relates to pharmaceutical engineering, and more particularly to a micro reaction system and a method for preparing 2-methyl-4-amino-5-cyanopyrimidine using the same. An acetamidine hydrochloride solution and an (dimethylaminomethylene)malononitrile solution are separately pumped into the micro reaction system including a micromixer and an agitating microchannel reactor in communication at the same time for a continuous condensation-cyclization reaction to obtain 2-methyl-4-amino-5-cyanopyrimidine.

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：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.