The present invention relates to a process for providing dihalogen substituted salicylic acid derivatives of formula (II): ##STR00001##

Methods of preparing a fenfluramine active pharmaceutical ingredient are provided. Aspects of the method include (a) hydrolyzing a 2-(3-(trifluoromethyl)phenyl)acetonitrile composition to produce a 2-(3-(trifluoromethyl)phenyl)acetic acid composition; (b) reacting the 2-(3-(trifluoromethyl)phenyl)acetic acid composition with acetic anhydride and a catalyst to produce a 1-(3-(trifluoromethyl)phenyl)propan-2-one composition; and (c) reductively aminating the 1-(3-(trifluoromethyl)phenyl)propan-2-one composition with ethylamine using a borohydride reducing agent to produce a fenfluramine composition. Also provided are compositions and pharmaceutical ingredients prepared according to the subject methods including a pharmaceutically acceptable salt of fenfluramine and having less than 0.2% by weight in total of trifluoromethyl regioisomers.

Methods of preparing a fenfluramine active pharmaceutical ingredient are provided. Aspects of the method include (a) hydrolyzing a 2-(3-(trifluoromethyl)phenyl)acetonitrile composition to produce a 2-(3-(trifluoromethyl)phenyl)acetic acid composition; (b) reacting the 2-(3-(trifluoromethyl)phenyl)acetic acid composition with acetic anhydride and a catalyst to produce a 1-(3-(trifluoromethyl)phenyl)propan-2-one composition; and (c) reductively aminating the 1-(3-(trifluoromethyl)phenyl)propan-2-one composition with ethylamine using a borohydride reducing agent to produce a fenfluramine composition. Also provided are compositions and pharmaceutical ingredients prepared according to the subject methods including a pharmaceutically acceptable salt of fenfluramine and having less than 0.2% by weight in total of trifluoromethyl regioisomers.

Methods of preparing a fenfluramine active pharmaceutical ingredient are provided. Aspects of the method include (a) hydrolyzing a 2-(3-(trifluoromethyl)phenyl)acetonitrile composition to produce a 2-(3-(trifluoromethyl)phenyl)acetic acid composition; (b) reacting the 2-(3-(trifluoromethyl)phenyl)acetic acid composition with acetic anhydride and a catalyst to produce a 1-(3-(trifluoromethyl)phenyl)propan-2-one composition; and (c) reductively aminating the 1-(3-(trifluoromethyl)phenyl)propan-2-one composition with ethylamine using a borohydride reducing agent to produce a fenfluramine composition. Also provided are compositions and pharmaceutical ingredients prepared according to the subject methods including a pharmaceutically acceptable salt of fenfluramine and having less than 0.2% by weight in total of trifluoromethyl regioisomers.

The present invention relates to Ras inhibitors and to methods for preparing Ras inhibitors.

The present invention relates to Ras inhibitors and to methods for preparing Ras inhibitors.

The invention relates to a thermal conversion vessel (200) used during amidification step of acetone cyanohydrin (ACH), in the industrial process for production of a methyl methacrylate (MMA) or methacrylic acid (MAA). The thermal conversion vessel (200) is used for converting an hydrolysis mixture of -hydroxyisobutyramide (HIBAM), -sulfatoisobutyramide (SIBAM), 2-methacrylamide (MACRYDE) and methacrylique acid (MAA), into a mixture of 2-methacrylamide (MACRYDE). It comprises: at least one compartment (C1, C2, C3, . . . Ci) comprising an inner wall (206a, 206b, 206i) separating said compartment into two communicating parts (C1a, C1b) by a passage provided between the bottom of said vessel and said inner wall, said compartment having a space above said inner wall, for separating gas phase from liquid phase during thermal conversion, said compartment being connected to an outlet valve (204a, 204b, . . . 204i).

Such vessel allows obtaining a high yield thermal conversion in very safe conditions.

The invention relates to a thermal conversion vessel (200) used during amidification step of acetone cyanohydrin (ACH), in the industrial process for production of a methyl methacrylate (MMA) or methacrylic acid (MAA). The thermal conversion vessel (200) is used for converting an hydrolysis mixture of -hydroxyisobutyramide (HIBAM), -sulfatoisobutyramide (SIBAM), 2-methacrylamide (MACRYDE) and methacrylique acid (MAA), into a mixture of 2-methacrylamide (MACRYDE). It comprises: at least one compartment (C1, C2, C3, . . . Ci) comprising an inner wall (206a, 206b, 206i) separating said compartment into two communicating parts (C1a, C1b) by a passage provided between the bottom of said vessel and said inner wall, said compartment having a space above said inner wall, for separating gas phase from liquid phase during thermal conversion, said compartment being connected to an outlet valve (204a, 204b, . . . 204i).

Such vessel allows obtaining a high yield thermal conversion in very safe conditions.

The invention relates to a thermal conversion vessel (200) used during amidification step of acetone cyanohydrin (ACH), in the industrial process for production of a methyl methacrylate (MMA) or methacrylic acid (MAA). The thermal conversion vessel (200) is used for converting an hydrolysis mixture of -hydroxyisobutyramide (HIBAM), -sulfatoisobutyramide (SIBAM), 2-methacrylamide (MACRYDE) and methacrylique acid (MAA), into a mixture of 2-methacrylamide (MACRYDE). It comprises: at least one compartment (C1, C2, C3, . . . Ci) comprising an inner wall (206a, 206b, 206i) separating said compartment into two communicating parts (C1a, C1b) by a passage provided between the bottom of said vessel and said inner wall, said compartment having a space above said inner wall, for separating gas phase from liquid phase during thermal conversion, said compartment being connected to an outlet valve (204a, 204b, . . . 204i).

Such vessel allows obtaining a high yield thermal conversion in very safe conditions.

The present invention pertains to a process for preparing 3-hydroxy-3-methylbutyric acid (HMB) or a salt thereof, the method comprising (a) reacting isobutylene oxide with cyanide in order to obtain 3-hydroxy-3-methylbutyronitrile, and (b) hydrolyzing the 3-hydroxy-3-methylbutyronitrile obtained in step (a) in order to obtain HMB, wherein hydrolysis step (b) is performed using either at least one nitrilase enzyme or, alternatively, using a combination of enzymes, said combination comprising at least one nitrile hydratase and at least one amidase.