The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure:

##STR00001## wherein A is an aryl or heteroaryl, each with or without substitution; and R.sub.1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), NH-(alkyl), N(alkyl).sub.2, NH-(alkenyl), NH-(alkynyl) NH-(aryl), NH-(heteroaryl), O-(alkyl), O-(alkenyl), O-(alkynyl), O-(aryl), O-(heteroaryl), S-(alkyl), S-(alkenyl), S-(alkynyl), S-(aryl), or S-(heteroaryl), comprising: (a) reacting a compound having the structure:

##STR00002## with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure:

##STR00003##

and (b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure:

##STR00004##

The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure:

##STR00001## wherein A is an aryl or heteroaryl, each with or without substitution; and R.sub.1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), NH-(alkyl), N(alkyl).sub.2, NH-(alkenyl), NH-(alkynyl) NH-(aryl), NH-(heteroaryl), O-(alkyl), O-(alkenyl), O-(alkynyl), O-(aryl), O-(heteroaryl), S-(alkyl), S-(alkenyl), S-(alkynyl), S-(aryl), or S-(heteroaryl), comprising: (a) reacting a compound having the structure:

##STR00002## with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure:

##STR00003##

and (b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure:

##STR00004##

The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure:

##STR00001## wherein A is an aryl or heteroaryl, each with or without substitution; and R.sub.1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), NH-(alkyl), N(alkyl).sub.2, NH-(alkenyl), NH-(alkynyl) NH-(aryl), NH-(heteroaryl), O-(alkyl), O-(alkenyl), O-(alkynyl), O-(aryl), O-(heteroaryl), S-(alkyl), S-(alkenyl), S-(alkynyl), S-(aryl), or S-(heteroaryl), comprising: (a) reacting a compound having the structure:

##STR00002## with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure:

##STR00003##

and (b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure:

##STR00004##

Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an intermediate of Formula 7. The third method utilizes a dibenzyl amine protecting group. ##STR00001## Also disclosed is a compound, phenylmethyl N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]carbamate (a compound of Formula 4). Further disclosed is a method for preparing a compound of Formula 14 from a compound of Formula 15 and a compound of Formula 1 or 1A. ##STR00002##

Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an intermediate of Formula 7. The third method utilizes a dibenzyl amine protecting group. ##STR00001## Also disclosed is a compound, phenylmethyl N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]carbamate (a compound of Formula 4). Further disclosed is a method for preparing a compound of Formula 14 from a compound of Formula 15 and a compound of Formula 1 or 1A. ##STR00002##

Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an intermediate of Formula 7. The third method utilizes a dibenzyl amine protecting group. ##STR00001## Also disclosed is a compound, phenylmethyl N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]carbamate (a compound of Formula 4). Further disclosed is a method for preparing a compound of Formula 14 from a compound of Formula 15 and a compound of Formula 1 or 1A. ##STR00002##

The present disclosure relates to a method for preparing various physiologically active pharmaceutical ingredients, such as a 1,1-diaryl compound and a 1,1-diheteroaryl compound (specifically, a 1,1-diaryl carbonyl compound), in an economical and convenient manner under mild conditions without using an expensive transition metal catalyst by activating an alkyne compound (e.g., an ynamide) using a Brnsted acid as a catalyst to induce a reaction of the activated alkyne compound and a NO bond oxidant to form an adduct intermediate and then inducing a coupling reaction of the adduct intermediate with various nucleophilic organic compounds (e.g., a nucleophilic arene compound).

The present disclosure relates to a method for preparing various physiologically active pharmaceutical ingredients, such as a 1,1-diaryl compound and a 1,1-diheteroaryl compound (specifically, a 1,1-diaryl carbonyl compound), in an economical and convenient manner under mild conditions without using an expensive transition metal catalyst by activating an alkyne compound (e.g., an ynamide) using a Brnsted acid as a catalyst to induce a reaction of the activated alkyne compound and a NO bond oxidant to form an adduct intermediate and then inducing a coupling reaction of the adduct intermediate with various nucleophilic organic compounds (e.g., a nucleophilic arene compound).

The present disclosure relates to a method for preparing various physiologically active pharmaceutical ingredients, such as a 1,1-diaryl compound and a 1,1-diheteroaryl compound (specifically, a 1,1-diaryl carbonyl compound), in an economical and convenient manner under mild conditions without using an expensive transition metal catalyst by activating an alkyne compound (e.g., an ynamide) using a Brnsted acid as a catalyst to induce a reaction of the activated alkyne compound and a NO bond oxidant to form an adduct intermediate and then inducing a coupling reaction of the adduct intermediate with various nucleophilic organic compounds (e.g., a nucleophilic arene compound).

The present invention relates to a process for synthesis of a compound according to Formula (A): wherein R.sub.1 is a substituted or unsubstituted aryl having 6 to 20 carbon atoms; preferably substituted or unsubstituted phenyl; R.sub.2 is a straight or branched alkyl having 1 to 12 carbon atoms; and R.sub.3 is a straight or branched alkyl having 1 to 12 carbon atoms; starting from a di-keto compound according to Formula (B) wherein R.sub.3 is as shown above, which compound is converted into a ketoenamine compound according to Formula (C) wherein R.sub.2 and R.sub.3 are as shown above, which ketoenamine compound is then reduced to an amino alcohol according to Formula (D), wherein R.sub.2 and R.sub.3 are as shown above, that is subsequently converted into a compound according to Formula (A): characterized in that the ketoenamine is reduced into an amino alcohol using a nickel aluminium alloy in an aqueous solution of an inorganic base.

##STR00001##