Processes for acylating an aromatic compound are provided. In embodiments, such a process comprises combining an aromatic compound, an acylating agent, and a catalyst composition under conditions to induce acylation of the aromatic compound with the acylating agent, the catalyst composition comprising components selected from the group consisting of a sulfonic acid of formula R—SO.sub.3H, wherein R is a linear alkyl group substituted with one or more halogen atoms; an ionic liquid and an acid; an acid and a base capable of forming an ionic liquid with the acid; an ionic liquid, an acid, and an aromatic; and an acid, a base capable of forming an ionic liquid with the acid, and an aromatic. The ionic liquid does not comprise a metal halide and the catalyst composition is free of a metal halide and the aromatic, if present in the catalyst composition, is not the aromatic compound being acylated.

A more environmentally friendly synthesis method of 4-bromo-2-(4′-ethoxyphenyl)-1-chlorobenzene with simplified steps provides a more effective synthetic strategy for producing key intermediates of SGLT-2 inhibitors such as dapagliflozin, sotagliflozin, and ertugliflozin. In the presence of trifluoroacetic anhydride, 5-bromo-2-chlorobenzoic acid and phenetole are selected to complete a direct acylation reaction under the catalysis of boron trifluoride diethyl etherate, and triethylsilane is added thereinto without treatment for one-pot reaction to obtain a target compound 4-bromo-2-(4′-ethoxyphenyl)-1-chlorobenzene.

A more environmentally friendly synthesis method of 4-bromo-2-(4′-ethoxyphenyl)-1-chlorobenzene with simplified steps provides a more effective synthetic strategy for producing key intermediates of SGLT-2 inhibitors such as dapagliflozin, sotagliflozin, and ertugliflozin. In the presence of trifluoroacetic anhydride, 5-bromo-2-chlorobenzoic acid and phenetole are selected to complete a direct acylation reaction under the catalysis of boron trifluoride diethyl etherate, and triethylsilane is added thereinto without treatment for one-pot reaction to obtain a target compound 4-bromo-2-(4′-ethoxyphenyl)-1-chlorobenzene.

The present disclosure provides a process for preparing an aryl ketone of Formula I, comprising reacting a substituted benzene of Formula II with a carboxylic acid of formula IIIa and/or a carboxylic anhydride of formula IIIb in presence of an alkyl sulfonic acid acting as catalyst cum solvent/contacting medium. I, II, IIIa, IIIb, wherein, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as defined in the description. ##STR00001##

A method for manufacturing 1,4-bis(4-phenoxybenzoyl)benzene, including: providing a solvent, a Lewis acid, a first reactant and a second reactant, wherein the first reactant and the second reactant are respectively terephthaloyl chloride and diphenyl ether, or reversely; mixing the first reactant in the solvent to make a starting mixture; and, adding the second reactant to the starting mixture; wherein the Lewis acid is mixed, at least partly, to the starting mixture before adding the second reactant to the starting mixture, and/or wherein the Lewis acid is mixed, at least partly, with the second reactant and added together to the starting mixture, and wherein the temperature of the starting mixture is greater than 5° C. during at least part of the step of adding the second reactant to the starting mixture; so as to obtain a product mixture comprising a 1,4-bis(4-phenoxybenzoyl)benzene-Lewis acid complex.

A method for manufacturing 1,4-bis(4-phenoxybenzoyl)benzene, including: providing a solvent, a Lewis acid, a first reactant and a second reactant, wherein the first reactant and the second reactant are respectively terephthaloyl chloride and diphenyl ether, or reversely; mixing the first reactant in the solvent to make a starting mixture; and, adding the second reactant to the starting mixture; wherein the Lewis acid is mixed, at least partly, to the starting mixture before adding the second reactant to the starting mixture, and/or wherein the Lewis acid is mixed, at least partly, with the second reactant and added together to the starting mixture, and wherein the temperature of the starting mixture is greater than 5° C. during at least part of the step of adding the second reactant to the starting mixture; so as to obtain a product mixture comprising a 1,4-bis(4-phenoxybenzoyl)benzene-Lewis acid complex.

A method for manufacturing 1,4-bis(4-phenoxybenzoyl)benzene, including: providing a solvent, a Lewis acid, a first reactant and a second reactant, wherein the first reactant and the second reactant are respectively terephthaloyl chloride and diphenyl ether, or reversely; mixing the first reactant in the solvent to make a starting mixture; and, adding the second reactant to the starting mixture; wherein the Lewis acid is mixed, at least partly, to the starting mixture before adding the second reactant to the starting mixture, and/or wherein the Lewis acid is mixed, at least partly, with the second reactant and added together to the starting mixture, and wherein the temperature of the starting mixture is greater than 5° C. during at least part of the step of adding the second reactant to the starting mixture; so as to obtain a product mixture comprising a 1,4-bis(4-phenoxybenzoyl)benzene-Lewis acid complex.

The invention relates to a process for preparing a compound of (III)

##STR00001## wherein X is a leaving group; and R.sup.1 is C.sub.1-C.sub.6 alkyl;
which comprises oxidative rearrangement of a compound of formula (II) or a solvate thereof

##STR00002##

Compounds of formula (III) are key intermediates in the synthesis of Bilastine.

The invention relates to a process for preparing a compound of (III)

##STR00001## wherein X is a leaving group; and R.sup.1 is C.sub.1-C.sub.6 alkyl;
which comprises oxidative rearrangement of a compound of formula (II) or a solvate thereof

##STR00002##

Compounds of formula (III) are key intermediates in the synthesis of Bilastine.

The invention relates to a process for preparing a compound of (III)

##STR00001## wherein X is a leaving group; and R.sup.1 is C.sub.1-C.sub.6 alkyl;
which comprises oxidative rearrangement of a compound of formula (II) or a solvate thereof

##STR00002##

Compounds of formula (III) are key intermediates in the synthesis of Bilastine.