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：US10961515B1

公开(公告)日：2021-03-30

申请号：US16904450

申请日：2020-06-17

Applicant: Fudan University

Inventor： Fener Chen ,  Zedu Huang ,  Zexu Wang ,  Minjie Liu

IPC: C12N9/04 ,  C12N1/20 ,  C12N15/52 ,  C12N15/70 ,  C12N15/74 ,  C12P7/62

Abstract: Disclosed herein are a carbonyl reductase variant and its use in the preparation of (R)-4-chloro-3-hydroxybutyrate. The carbonyl reductase variant is obtained by mutating phenylalanine-85 in an amino acid sequence as shown in SEQ ID NO:4 to methionine. An amino acid or amino acids at one or more positions other than position 85 in the amino acid sequence of the carbonyl reductase may be further replaced. The application also provides a recombinant expression vector carrying the gene encoding the carbonyl reductase variant, a genetically-engineered bacterium carrying the carbonyl reductase variant gene and glucose dehydrogenase gene, and an application of this bacterium in the asymmetric reduction of 4-chloroacetoacetate to prepare (R)-4-chloro-3-hydroxybutyrate.

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.