The invention relates to a multi-stage process for preparing 2,6-dialkylphenylacetic acids of the general formula (I) by reacting 2,6-dialkylbromobenzenes with (1) magnesium, (2) a formamide, (3) an acid, (4) hydrogenation of the benzaldehyde obtained, (5) activation of the benzyl alcohol obtained, (6) cyanation of the activated benzyl alcohol and (7) hydrolysis of the nitrile obtained.

The invention relates to a multi-stage process for preparing 2,6-dialkylphenylacetic acids of the general formula (I) by reacting 2,6-dialkylbromobenzenes with (1) magnesium, (2) a formamide, (3) an acid, (4) hydrogenation of the benzaldehyde obtained, (5) activation of the benzyl alcohol obtained, (6) cyanation of the activated benzyl alcohol and (7) hydrolysis of the nitrile obtained.

The invention relates to a multi-stage process for preparing 2,6-dialkylphenylacetic acids of the general formula (I) by reacting 2,6-dialkylbromobenzenes with (1) magnesium, (2) a formamide, (3) an acid, (4) hydrogenation of the benzaldehyde obtained, (5) activation of the benzyl alcohol obtained, (6) cyanation of the activated benzyl alcohol and (7) hydrolysis of the nitrile obtained.

A glycolic acid salt that can be a raw material (intermediate product) for producing glycolic acid is more efficiently produced by a simple process. A method for producing a glycolic acid salt includes step (1) of reacting at least one compound selected from the group consisting of glycolonitrile and glycolamide with water in the presence of a metal oxide containing 50% by mass or more of at least one element selected from the group consisting of a rare earth element, a group 4 element of the periodic table, and a group 12 element of the periodic table, and a base to obtain a glycolic acid salt.

A glycolic acid salt that can be a raw material (intermediate product) for producing glycolic acid is more efficiently produced by a simple process. A method for producing a glycolic acid salt includes step (1) of reacting at least one compound selected from the group consisting of glycolonitrile and glycolamide with water in the presence of a metal oxide containing 50% by mass or more of at least one element selected from the group consisting of a rare earth element, a group 4 element of the periodic table, and a group 12 element of the periodic table, and a base to obtain a glycolic acid salt.

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.

This disclosure generally relates to methods of making ibuprofen, naproxen, and derivatives thereof. This disclosure also generally relates to compounds made by the disclosed methods. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

This disclosure generally relates to methods of making ibuprofen, naproxen, and derivatives thereof. This disclosure also generally relates to compounds made by the disclosed methods. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.