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    METHOD FOR CONTINUOUSLY PRODUCING A PRODUCT BY WAY OF AT LEAST TWO COUPLED-TOGETHER CHEMICAL REACTIONS
    6.
    发明申请
    METHOD FOR CONTINUOUSLY PRODUCING A PRODUCT BY WAY OF AT LEAST TWO COUPLED-TOGETHER CHEMICAL REACTIONS 审中-公开

    公开(公告)号：US20200301452A1

    公开(公告)日：2020-09-24

    申请号：US16878923

    申请日：2020-05-20

    申请人： Covestro Deutschland AG

    发明人： Bernd Pennemann ,  Erwin Dieterich ,  Heinz-Josef Hamacher

    IPC分类号： G05D7/06 ,  C07C201/08 ,  B01J19/00 ,  F16K31/02

    摘要： A method for continuously producing a product (A1) by way of at least two coupled-together chemical reactions (C1, C2), wherein at least two input substances (E1, E2) are fed to a first chemical reaction (C1), wherein a plurality of intermediate substances (Z1, Z2) are produced from the input substances (E1, E2) by the first chemical reaction (C1), wherein at least one of the intermediate substances (Z2) is fed to a second chemical reaction (C2), wherein the at least one fed intermediate substance (Z2) is further processed by the second chemical reaction (C2), in particular using at least one further substance (W1, W2) in a second chemical reaction (C2) to form a plurality of output substances (A1, A2), that is to say to form the chemical product (A1) and at least one further output substance (A2), wherein the flow rates (Fi) of the fed substances (E1, E2, Z1, W1, W2, A2) that are fed to one of the reactions (C1, C2) are set by a respective actuating element (VE1, VE2, VW1, VW 2, VZ 2, VA1), wherein each of the fed substances is assigned a separate actuating element, wherein a manipulated variable (SE2,R, Si,R) that is stipulated by a controller (RE2, Ri) is respectively applied to at least one of the actuating elements, wherein, for changing the production rate of the chemical product (A1), a temporary manipulated variable (SE2,temp, Si,temp) is respectively applied during a transient phase (II, III) to at least one of these actuating elements (VE2, Vi) instead of the manipulated variables (SE2, R, Si,R) stipulated by the respective controllers (RE2, Ri), wherein the temporary manipulated variable (SE2,temp, Si,temp) or the temporary manipulated variables is/are generated by at least one control unit (SE) in dependence on a default value (NV).

    METHOD OF SYNTHESIZING DICLOFENAC SODIUM
    7.
    发明申请
    METHOD OF SYNTHESIZING DICLOFENAC SODIUM 审中-公开

    公开(公告)号：US20200055811A1

    公开(公告)日：2020-02-20

    申请号：US16288031

    申请日：2019-02-27

    申请人： FUDAN UNIVERSITY

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

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

    摘要： 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.