A process for the preparation of 1-bromo-2,4,5-trifluorobenzene from 2,4,5-trifluoroaniline or sulfate salt thereof.

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A process for the preparation of 1 ,2,4-trifluorobenzene from 2,4,5-trifluoroaniline and then converting into 1-bromo-2,4,5-trifluorobenzene.

The invention relates to a use of a fluorination gas, the elemental fluorine (F.sub.2) is preferably present in a high concentration, e.g. in a concentration of elemental fluorine (F.sub.2), especially of equal to much higher than 15% or even 20% by volume (i.e., at least 15% or even 20% by volume), and to a process for the manufacture of a fluorinated benzene starting from benzoic acid by direct fluorination employing a fluorination gas. The elemental fluorine (F.sub.2) is preferably present in high concentration, and subsequent decarboxylation of the benzoic acid hypofluorite obtained by direct fluorination. The process of the invention is also directed to the manufacture of benzoic acid hypofluorite by direct fluorination of benzoic acid. Especially the invention is of interest in the preparation of fluorinatedbenzene, final products and as well intermediates, for usage in agro-, pharma-, electronics-, catalyst, solvent and other functional chemical applications.

The invention relates to a use of a fluorination gas, the elemental fluorine (F.sub.2) is preferably present in a high concentration, e.g. in a concentration of elemental fluorine (F.sub.2), especially of equal to much higher than 15% or even 20% by volume (i.e., at least 15% or even 20% by volume), and to a process for the manufacture of a fluorinated benzene starting from benzoic acid by direct fluorination employing a fluorination gas. The elemental fluorine (F.sub.2) is preferably present in high concentration, and subsequent decarboxylation of the benzoic acid hypofluorite obtained by direct fluorination. The process of the invention is also directed to the manufacture of benzoic acid hypofluorite by direct fluorination of benzoic acid. Especially the invention is of interest in the preparation of fluorinatedbenzene, final products and as well intermediates, for usage in agro-, pharma-, electronics-, catalyst, solvent and other functional chemical applications.

The invention relates to a use of a fluorination gas, the elemental fluorine (F.sub.2) is preferably present in a high concentration, e.g. in a concentration of elemental fluorine (F.sub.2), especially of equal to much higher than 15% or even 20% by volume (i.e., at least 15% or even 20% by volume), and to a process for the manufacture of a fluorinated benzene starting from benzoic acid by direct fluorination employing a fluorination gas. The elemental fluorine (F.sub.2) is preferably present in high concentration, and subsequent decarboxylation of the benzoic acid hypofluorite obtained by direct fluorination. The process of the invention is also directed to the manufacture of benzoic acid hypofluorite by direct fluorination of benzoic acid. Especially the invention is of interest in the preparation of fluorinatedbenzene, final products and as well intermediates, for usage in agro-, pharma-, electronics-, catalyst, solvent and other functional chemical applications.

The present invention relates to an improved process for the preparation of enzalutamide by conventional synthesis, which avoids utilization of microwave irradiation and noxious reagents. The present invention also relates to an improved process for preparation of 4-isothiocyanato-2-(trifluoromethyl) benzonitrile, which is an intermediate in the synthesis of Enzalutamide.

The present invention relates to an improved process for the preparation of enzalutamide by conventional synthesis, which avoids utilization of microwave irradiation and noxious reagents. The present invention also relates to an improved process for preparation of 4-isothiocyanato-2-(trifluoromethyl) benzonitrile, which is an intermediate in the synthesis of Enzalutamide.

An object of the present invention is to enable the synthesis of various fluorine-containing compounds having an organic group at both terminals of their tetrafluoroethylene structure (—CF.sub.2—CF.sub.2—). The present invention provides a fluorine-containing complex compound including a fluorine-containing organic metal compound represented by formula (1a):
R.sup.1—CF.sub.2—CF.sub.2-M.sup.1  (1a)
wherein M.sup.1 is a metal selected from the group consisting of copper, zinc, nickel, iron, cobalt, and tin; and R.sup.1 represents an organic group, and at least one ligand selected from the group consisting of pyridine ring-containing compounds and phosphines.

An object of the present invention is to enable the synthesis of various fluorine-containing compounds having an organic group at both terminals of their tetrafluoroethylene structure (—CF.sub.2—CF.sub.2—). The present invention provides a fluorine-containing complex compound including a fluorine-containing organic metal compound represented by formula (1a):
R.sup.1—CF.sub.2—CF.sub.2-M.sup.1  (1a)
wherein M.sup.1 is a metal selected from the group consisting of copper, zinc, nickel, iron, cobalt, and tin; and R.sup.1 represents an organic group, and at least one ligand selected from the group consisting of pyridine ring-containing compounds and phosphines.

Disclosed is a method for synthesizing a sitagliptin intermediate, the method comprising: in the presence of hydrogen and a transition metal catalyst having a chiral phosphine ligand, subjecting a compound of formula II to an asymmetric reductive amination with ammonia or ammonium salt in a proper organic solvent under the condition of adding an acidic additive to produce a compound of formula I, wherein, an R- or S-configuration of a stereocenter is represented by *; the compound of formula I of R configuration can be used to prepare sitagliptin, and a reaction formula is as follows: R.sup.1 and R.sup.2 are each independently selected from hydrogen, C.sub.1-C.sub.12 linear or branched alkyl, C.sub.3-C.sub.12 cycloalkyl, C.sub.2-C.sub.12 alkenyl, C.sub.2-C.sub.12 alkynyl and C.sub.7-C.sub.12 arylalkyl. The method has a high yield and a high ee % value, a mild reaction condition and a low production cost, and is simple to operate, convenient to purify, environmental friendly and suitable for industrial production.

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Disclosed is a method for synthesizing a sitagliptin intermediate, the method comprising: in the presence of hydrogen and a transition metal catalyst having a chiral phosphine ligand, subjecting a compound of formula II to an asymmetric reductive amination with ammonia or ammonium salt in a proper organic solvent under the condition of adding an acidic additive to produce a compound of formula I, wherein, an R- or S-configuration of a stereocenter is represented by *; the compound of formula I of R configuration can be used to prepare sitagliptin, and a reaction formula is as follows: R.sup.1 and R.sup.2 are each independently selected from hydrogen, C.sub.1-C.sub.12 linear or branched alkyl, C.sub.3-C.sub.12 cycloalkyl, C.sub.2-C.sub.12 alkenyl, C.sub.2-C.sub.12 alkynyl and C.sub.7-C.sub.12 arylalkyl. The method has a high yield and a high ee % value, a mild reaction condition and a low production cost, and is simple to operate, convenient to purify, environmental friendly and suitable for industrial production.

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