An object of the present invention is to remove a compound A from sevoflurane containing fluoromethyl-1,1,3,3,3-pentafluoroisopropenyl ether (compound A) so as to collect high-purity sevoflurane. The present invention concerns a method for producing sevoflurane containing substantially no compound A, comprising the following steps of: bringing a composition containing hydrogen fluoride (HF) and water at a mass ratio of 1:1 to 1:30 into contact with a 1st organic liquid containing sevoflurane and a compound A, thereby obtaining a 2nd organic liquid containing the compound A in an amount that is lower than that in the 1st organic liquid (step 1a); and distilling the 2nd organic liquid under the presence of a degradation inhibitor, thereby obtaining sevoflurane containing substantially no compound A as a main distillation fraction (step 2).

An object of the present invention is to remove a compound A from sevoflurane containing fluoromethyl-1,1,3,3,3-pentafluoroisopropenyl ether (compound A) so as to collect high-purity sevoflurane. The present invention concerns a method for producing sevoflurane containing substantially no compound A, comprising the following steps of: bringing a composition containing hydrogen fluoride (HF) and water at a mass ratio of 1:1 to 1:30 into contact with a 1st organic liquid containing sevoflurane and a compound A, thereby obtaining a 2nd organic liquid containing the compound A in an amount that is lower than that in the 1st organic liquid (step 1a); and distilling the 2nd organic liquid under the presence of a degradation inhibitor, thereby obtaining sevoflurane containing substantially no compound A as a main distillation fraction (step 2).

An object of the present invention is to remove a compound A from sevoflurane containing fluoromethyl-1,1,3,3,3-pentafluoroisopropenyl ether (compound A) so as to collect high-purity sevoflurane. The present invention concerns a method for producing sevoflurane containing substantially no compound A, comprising the following steps of: bringing a composition containing hydrogen fluoride (HF) and water at a mass ratio of 1:1 to 1:30 into contact with a 1st organic liquid containing sevoflurane and a compound A, thereby obtaining a 2nd organic liquid containing the compound A in an amount that is lower than that in the 1st organic liquid (step 1a); and distilling the 2nd organic liquid under the presence of a degradation inhibitor, thereby obtaining sevoflurane containing substantially no compound A as a main distillation fraction (step 2).

An object of the present invention is to remove a compound A from sevoflurane containing fluoromethyl-1,1,3,3,3-pentafluoroisopropenyl ether (compound A) so as to collect high-purity sevoflurane. The present invention concerns a method for producing sevoflurane containing substantially no compound A, comprising the following steps of: bringing a composition containing hydrogen fluoride (HF) and water at a mass ratio of 1:1 to 1:30 into contact with a 1st organic liquid containing sevoflurane and a compound A, thereby obtaining a 2nd organic liquid containing the compound A in an amount that is lower than that in the 1st organic liquid (step 1a); and distilling the 2nd organic liquid under the presence of a degradation inhibitor, thereby obtaining sevoflurane containing substantially no compound A as a main distillation fraction (step 2).

A method of purifying crude sevoflurane comprising (i) providing crude sevoflurane and an aqueous base to a first centrifugal separator, wherein the crude sevoflurane comprises sevoflurane and hexafluoroisopropanol; (ii) mixing the crude sevoflurane and the aqueous base in the first centrifugal separator; and (iii) separating the sevoflurane from the aqueous base in the first centrifugal separator, thereby purifying the crude sevoflurane.

A method of purifying crude sevoflurane comprising (i) providing crude sevoflurane and an aqueous base to a first centrifugal separator, wherein the crude sevoflurane comprises sevoflurane and hexafluoroisopropanol; (ii) mixing the crude sevoflurane and the aqueous base in the first centrifugal separator; and (iii) separating the sevoflurane from the aqueous base in the first centrifugal separator, thereby purifying the crude sevoflurane.

The present invention provides processes for preparing a prostacyclin analogue of Formula I

##STR00001##

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

##STR00001##

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 disclosure provides a method for isolating dialkylene phenolic glycol ether (DPGE) from a mixture that includes DPGE and glycosylated phenol impurities. The method includes adding a source of an alkali metal to the mixture to form a phenolic glycol product having an alkali phenolic salt formed from a reaction between the alkali metal and the glycosylated phenol impurities; and separating the DPGE from the alkali phenolic salt in the phenolic glycol product through a thin film evaporation process to produce a dialkylene phenolic glycol ether product. The disclosure also includes a phenolic glycol product that includes DPGE; water; glycosylated phenol impurities; a source of alkali metal; and an alkali phenolic salt formed from a reaction between the alkali metal and the glycosylated phenol impurities.

The present disclosure provides a method for isolating dialkylene phenolic glycol ether (DPGE) from a mixture that includes DPGE and glycosylated phenol impurities. The method includes adding a source of an alkali metal to the mixture to form a phenolic glycol product having an alkali phenolic salt formed from a reaction between the alkali metal and the glycosylated phenol impurities; and separating the DPGE from the alkali phenolic salt in the phenolic glycol product through a thin film evaporation process to produce a dialkylene phenolic glycol ether product. The disclosure also includes a phenolic glycol product that includes DPGE; water; glycosylated phenol impurities; a source of alkali metal; and an alkali phenolic salt formed from a reaction between the alkali metal and the glycosylated phenol impurities.