The invention provides a new process for the preparation of treprostinil of formula (I) and its salts using several new intermediates during the building of the ring system.

##STR00001##

A method of preparing a difluorinated alcohol compound is provided. The difluorinated alcohol compound can be easily synthesized when an aldehyde and N-fluorobenzenesulfonimide are reacted in the presence of L-proline, and thus the method has advantage in that preparation processes are simple and reagents are economical and safe, compared to the related-art methods. Therefore, the preparation method can be effectively applied to prepare a difluorinated alcohol used in various applications for raw materials such as functional medicines, agricultural chemicals, polymerizable compounds, etc.

A method of preparing a difluorinated alcohol compound is provided. The difluorinated alcohol compound can be easily synthesized when an aldehyde and N-fluorobenzenesulfonimide are reacted in the presence of L-proline, and thus the method has advantage in that preparation processes are simple and reagents are economical and safe, compared to the related-art methods. Therefore, the preparation method can be effectively applied to prepare a difluorinated alcohol used in various applications for raw materials such as functional medicines, agricultural chemicals, polymerizable compounds, etc.

A method of preparing a difluorinated alcohol compound is provided. The difluorinated alcohol compound can be easily synthesized when an aldehyde and N-fluorobenzenesulfonimide are reacted in the presence of L-proline, and thus the method has advantage in that preparation processes are simple and reagents are economical and safe, compared to the related-art methods. Therefore, the preparation method can be effectively applied to prepare a difluorinated alcohol used in various applications for raw materials such as functional medicines, agricultural chemicals, polymerizable compounds, etc.

A process for transitioning a reactor from base-catalyzed polyol production to double metal cyanide (DMC)-catalyzed polyol production is described. The process includes discharging a base-catalyzed and un-neutralized product mixture from a reactor, and adding an acidified polyether polyol starter and DMC catalyst mixture to the reactor. A DMC-catalyzed polyol production reaction can then be conducted in the reactor without intermediate washing or rinsing of the reactor, and without catalyst deactivation from base or alkaline hold-up.

A process for transitioning a reactor from base-catalyzed polyol production to double metal cyanide (DMC)-catalyzed polyol production is described. The process includes discharging a base-catalyzed and un-neutralized product mixture from a reactor, and adding an acidified polyether polyol starter and DMC catalyst mixture to the reactor. A DMC-catalyzed polyol production reaction can then be conducted in the reactor without intermediate washing or rinsing of the reactor, and without catalyst deactivation from base or alkaline hold-up.

The present invention provides processes for preparing a prostacyclin analogue of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R.sup.10 is a linear or branched C.sub.1-6 alkyl. The processes of the present invention comprise steps that generate improved yields and fewer byproducts than traditional methods. The processes of the present invention employ reagents (e.g., the oxidizing reagent) that are less toxic that those used in the traditional methods (e.g., oxalyl chloride). Many of the processes of the present invention generate intermediates with improved e.e. and chemical purity; thereby eliminating the need of additional chromatography steps. And, the processes of the present invention are scalable to generate commercial quantities of the final compound.

The present invention provides processes for preparing a prostacyclin analogue of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R.sup.10 is a linear or branched C.sub.1-6 alkyl. The processes of the present invention comprise steps that generate improved yields and fewer byproducts than traditional methods. The processes of the present invention employ reagents (e.g., the oxidizing reagent) that are less toxic that those used in the traditional methods (e.g., oxalyl chloride). Many of the processes of the present invention generate intermediates with improved e.e. and chemical purity; thereby eliminating the need of additional chromatography steps. And, the processes of the present invention are scalable to generate commercial quantities of the final compound.

The present invention provides processes for preparing a prostacyclin analogue of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R.sup.10 is a linear or branched C.sub.1-6 alkyl. The processes of the present invention comprise steps that generate improved yields and fewer byproducts than traditional methods. The processes of the present invention employ reagents (e.g., the oxidizing reagent) that are less toxic that those used in the traditional methods (e.g., oxalyl chloride). Many of the processes of the present invention generate intermediates with improved e.e. and chemical purity; thereby eliminating the need of additional chromatography steps. And, the processes of the present invention are scalable to generate commercial quantities of the final compound.

We provide a novel and useful process for preparing triphenyl-butene derivative. A process for the preparation of a compound represented by Formula (IV):

##STR00001##

wherein R.sup.1 is hydrogen or substituted or unsubstituted alkyl,
characterized by reacting a compound represented by Formula (V):

##STR00002##

with a compound represented by Formula (VI):

##STR00003##

wherein R.sup.1 has the same meaning as defined above,
in the presence of 1) a polyvalent metal chloride, 2) a reducing agent and 3) an alkali metal salt and/or a substituted or unsubstituted phenol.