The present disclosure relates generally to compounds which bind to the NR1H4 receptor (FXR) and act as agonists of FXR. The disclosure further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds and to a process for the synthesis of said compounds.

The present disclosure relates generally to compounds which bind to the NR1H4 receptor (FXR) and act as agonists of FXR. The disclosure further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds and to a process for the synthesis of said compounds.

The invention relates to a use of a fluorination gas, and the elemental fluorine (F.sub.2) is present in a high concentration, for example, in a concentration of elemental fluorine (F.sub.2), especially of equal to much higher than 15 or even 20% by volume, and to a process for the manufacture of a fluorinated compound by direct fluorination employing a fluorination gas, wherein the elemental fluorine (F.sub.2) is present in a high concentration. The process of the invention is directed to the manufacture of a fluorinated compound, for the exception of fluorinated benzene, by direct fluorination. Especially the invention is of interest in the preparation of fluorinated organic compounds, final products and as well intermediates, for usage in agro-, pharma-, electronics-, catalyst, solvent and other functional chemical applications. The fluorination process of the invention may be performed batch-wise or in a continuous manner.

The invention relates to a use of a fluorination gas, and the elemental fluorine (F.sub.2) is present in a high concentration, for example, in a concentration of elemental fluorine (F.sub.2), especially of equal to much higher than 15 or even 20% by volume, and to a process for the manufacture of a fluorinated compound by direct fluorination employing a fluorination gas, wherein the elemental fluorine (F.sub.2) is present in a high concentration. The process of the invention is directed to the manufacture of a fluorinated compound, for the exception of fluorinated benzene, by direct fluorination. Especially the invention is of interest in the preparation of fluorinated organic compounds, final products and as well intermediates, for usage in agro-, pharma-, electronics-, catalyst, solvent and other functional chemical applications. The fluorination process of the invention may be performed batch-wise or in a continuous manner.

The invention relates to process for the manufacture or preparation of fluorinated benzene, in particular monofluorobenzene, in a vapor-phase fluorination process. The process of the invention, for example, can comprise a batch or continuous manufacture or preparation of fluorinated benzene, in particular monofluorobenzene, using hydrogen fluoride (HF) in gas phase as fluorination gas. Also, in this process of the invention, for example, fluorination catalysts are involved.

The invention relates to process for the manufacture or preparation of fluorinated benzene, in particular monofluorobenzene, in a vapor-phase fluorination process. The process of the invention, for example, can comprise a batch or continuous manufacture or preparation of fluorinated benzene, in particular monofluorobenzene, using hydrogen fluoride (HF) in gas phase as fluorination gas. Also, in this process of the invention, for example, fluorination catalysts are involved.

Disclosed is a fluorination method comprising providing an aryl fluorosulfonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosulfonate and the fluorinating reagent to provide a fluorinated aryl species. Also disclosed is a fluorination method comprising providing, a salt comprising a cation and an aryloxylate, and SO.sub.2F.sub.2 to a reaction mixture; reacting the SO.sub.2F.sub.2 and the ammonium salt to provide a fluorinated aryl species. Further disclosed a fluorination method comprising providing a compound having the structure Ar—OH to a reaction mixture; where Ar is an aryl or heteroaryl; providing SO.sub.2F.sub.2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO.sub.2F.sub.2, the fluorinating reagent and the compound having the structure Ar—OH to provide a fluorinated aryl species having the structure Ar—F.

Disclosed is a fluorination method comprising providing an aryl fluorosulfonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosulfonate and the fluorinating reagent to provide a fluorinated aryl species. Also disclosed is a fluorination method comprising providing, a salt comprising a cation and an aryloxylate, and SO.sub.2F.sub.2 to a reaction mixture; reacting the SO.sub.2F.sub.2 and the ammonium salt to provide a fluorinated aryl species. Further disclosed a fluorination method comprising providing a compound having the structure Ar—OH to a reaction mixture; where Ar is an aryl or heteroaryl; providing SO.sub.2F.sub.2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO.sub.2F.sub.2, the fluorinating reagent and the compound having the structure Ar—OH to provide a fluorinated aryl species having the structure Ar—F.

Disclosed is a fluorination method comprising providing an aryl fluorosulfonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosulfonate and the fluorinating reagent to provide a fluorinated aryl species. Also disclosed is a fluorination method comprising providing, a salt comprising a cation and an aryloxylate, and SO.sub.2F.sub.2 to a reaction mixture; reacting the SO.sub.2F.sub.2 and the ammonium salt to provide a fluorinated aryl species. Further disclosed a fluorination method comprising providing a compound having the structure Ar—OH to a reaction mixture; where Ar is an aryl or heteroaryl; providing SO.sub.2F.sub.2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO.sub.2F.sub.2, the fluorinating reagent and the compound having the structure Ar—OH to provide a fluorinated aryl species having the structure Ar—F.

The present invention provides PC.sub.NHCP pincer metal complexes, which are useful as catalysts in various chemical reactions such as hydrogen isotope exchange (HIE) in C(sp.sup.3)-H and/or C(sp.sup.2)-H bond of an organic compound, e.g., a pharmaceutically active compound; hydroboration of alkynes with excellent selectivity; and alkene isomerization with high stereo- and regioselectivity.