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.

A production method by which a biarylphosphine useful as a Buchwald phosphine ligand can be obtained in high purity is provided through an industrially advantageous process. The production method of a biarylphosphine comprises a step A of reacting a lithiated product obtained through lithiation of a halogenated benzene derivative with a benzene derivative to obtain a biphenyl derivative, and a step B of the reacting the biphenyl derivative with a halogenated phosphine. In the step A, the charge molar ratio of the halogenated benzene derivative to the benzene derivative is preferably 1.0 to 5.0.

A production method by which a biarylphosphine useful as a Buchwald phosphine ligand can be obtained in high purity is provided through an industrially advantageous process. The production method of a biarylphosphine comprises a step A of reacting a lithiated product obtained through lithiation of a halogenated benzene derivative with a benzene derivative to obtain a biphenyl derivative, and a step B of the reacting the biphenyl derivative with a halogenated phosphine. In the step A, the charge molar ratio of the halogenated benzene derivative to the benzene derivative is preferably 1.0 to 5.0.

This invention relates to a chemistry branch, particularly to the field of compounds' organic synthesis that belongs to the aromatic bicyclic or naphthalene category, used in the detection of amyloid sheets. These new naphthalene derivatives have a general formula: Wherein R represents mutually independent groups. In I: R.sub.1:-alkylenyl-C(O)NH-alkylenyl-R.sub.3, -alkylenyl-C(O)O—R.sub.4, R.sub.3:—COOH, —OH, —SH, —NH.sub.2, -alkyl-NH-alkyl-N-dithiocarbamate alkaline earth metal salts, R.sub.4: H, succinimidyl group, R.sub.2: —H,-alkyl. In II: R.sub.1: -alkyl, -alkylenyl-halide-alkylenyl-hydroxyl-alkylenyl-O-aryl, —O-alkylsulfonate alkylenyl, R.sub.2: -halide-alkylenyl-O-aryl, -alkylenyl-O-alkylsulfonate, -alkylenyl-halide-, —CH(O), —HC═C(CN).sub.2, —HC═CHNO.sub.2, -alkylenyl-NH.sub.2, -alkylenyl-NH-alkyl, -alkylenyl-alkyl-N-dithiocarbamate alkaline salts. The terms “alkyl” and “alkylenyl” refer to linear or branched aliphatic chains, preferably from 1 to 4 carbon atoms and the term halide to fluorine, bromine or iodine. These compounds are neutral, lipophilic and have low molecular weight and therefore they cross the blood brain barrier and attach to the amyloid sheets. The present invention provides procedures for obtaining naphthalene derivatives with good yields, which can be practical, economical and adapted to a larger-scale manufacturing. We are unaware whether the compounds presented in this invention have been previously reported.

This invention relates to a chemistry branch, particularly to the field of compounds' organic synthesis that belongs to the aromatic bicyclic or naphthalene category, used in the detection of amyloid sheets. These new naphthalene derivatives have a general formula: Wherein R represents mutually independent groups. In I: R.sub.1:-alkylenyl-C(O)NH-alkylenyl-R.sub.3, -alkylenyl-C(O)O—R.sub.4, R.sub.3:—COOH, —OH, —SH, —NH.sub.2, -alkyl-NH-alkyl-N-dithiocarbamate alkaline earth metal salts, R.sub.4: H, succinimidyl group, R.sub.2: —H,-alkyl. In II: R.sub.1: -alkyl, -alkylenyl-halide-alkylenyl-hydroxyl-alkylenyl-O-aryl, —O-alkylsulfonate alkylenyl, R.sub.2: -halide-alkylenyl-O-aryl, -alkylenyl-O-alkylsulfonate, -alkylenyl-halide-, —CH(O), —HC═C(CN).sub.2, —HC═CHNO.sub.2, -alkylenyl-NH.sub.2, -alkylenyl-NH-alkyl, -alkylenyl-alkyl-N-dithiocarbamate alkaline salts. The terms “alkyl” and “alkylenyl” refer to linear or branched aliphatic chains, preferably from 1 to 4 carbon atoms and the term halide to fluorine, bromine or iodine. These compounds are neutral, lipophilic and have low molecular weight and therefore they cross the blood brain barrier and attach to the amyloid sheets. The present invention provides procedures for obtaining naphthalene derivatives with good yields, which can be practical, economical and adapted to a larger-scale manufacturing. We are unaware whether the compounds presented in this invention have been previously reported.

A composition, consisting essentially of copper, a fluoroalkyl group, and a ligand comprising at least one group-V donor. The molar ratio of copper to the fluoroalkyl group is approximately 1.

A composition, consisting essentially of copper, a fluoroalkyl group, and a ligand comprising at least one group-V donor. The molar ratio of copper to the fluoroalkyl group is approximately 1.

Object: An object of the present invention is to provide a method for producing, with a high yield, a fluorinated organic compound, the fluorinated organic compound having not been produced with a sufficient yield by a conventional method for producing a fluorinated organic compound using a fluorinating agent containing IF.sub.5-pyridine-HF alone. Another object of the present invention is to provide a fluorinating reagent. Means for achieving the object: A method for producing a fluorinated organic compound comprising step A of fluorinating an organic compound by bringing the organic compound into contact with (1) IF.sub.5-pyridine-HF and (2) at least one additive selected from the group consisting of amine hydrogen fluorides, X.sup.aF (wherein X.sup.a represents hydrogen, potassium, sodium, or lithium), oxidizers, and reducing agents.

Object: An object of the present invention is to provide a method for producing, with a high yield, a fluorinated organic compound, the fluorinated organic compound having not been produced with a sufficient yield by a conventional method for producing a fluorinated organic compound using a fluorinating agent containing IF.sub.5-pyridine-HF alone. Another object of the present invention is to provide a fluorinating reagent. Means for achieving the object: A method for producing a fluorinated organic compound comprising step A of fluorinating an organic compound by bringing the organic compound into contact with (1) IF.sub.5-pyridine-HF and (2) at least one additive selected from the group consisting of amine hydrogen fluorides, X.sup.aF (wherein X.sup.a represents hydrogen, potassium, sodium, or lithium), oxidizers, and reducing agents.