A chemical reaction is catalyzed in an organic solvent using a water soluble N-heterocyclic carbene homogeneous catalyst to form a reaction mixture. An aqueous phase in the reaction mixture. A solvent in which the catalyst is insoluble is added to the reaction mixture, causing the catalyst to migrate to the aqueous phase to form a catalyst-laden aqueous phase. The catalyst is extracted from the catalyst-laden aqueous phase.

A chemical reaction is catalyzed in an organic solvent using a water soluble N-heterocyclic carbene homogeneous catalyst to form a reaction mixture. An aqueous phase in the reaction mixture. A solvent in which the catalyst is insoluble is added to the reaction mixture, causing the catalyst to migrate to the aqueous phase to form a catalyst-laden aqueous phase. The catalyst is extracted from the catalyst-laden aqueous phase.

A chemical reaction is catalyzed in an organic solvent using a water soluble N-heterocyclic carbene homogeneous catalyst to form a reaction mixture. An aqueous phase in the reaction mixture. A solvent in which the catalyst is insoluble is added to the reaction mixture, causing the catalyst to migrate to the aqueous phase to form a catalyst-laden aqueous phase. The catalyst is extracted from the catalyst-laden aqueous phase.

The invention provides a new convergent approach for the synthesis of 2-fluoro-6-methylene-carbocyclic adenosine (FMCA) and 2-fluoro-6-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R, 4R)-3-tert-butoxy -4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.

The invention provides a new convergent approach for the synthesis of 2-fluoro-6-methylene-carbocyclic adenosine (FMCA) and 2-fluoro-6-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R, 4R)-3-tert-butoxy -4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.

The present invention relates to an unsaturated fluorinated ether or amine compound of formula (I) with low global warming potential and method of making the compound (I), where R.sub.H.sup.1 is and R.sub.H.sup.2 are independently selected from H or CH.sub.3, wherein when R.sub.H.sup.1 is CH.sub.3 then R.sub.H.sup.2 is H and when R.sub.H.sup.2 is CH.sub.3, then R.sub.H.sup.1 is H; X is O or N and when X is O, then n is 1 and R.sub.f is a linear or branched perfluorinated alkyl group comprising 1-10 carbon atoms and optionally comprising at least one catenated O or N atom; X is N, then n is 2 and (i) each R.sub.f is independently selected from a linear or branched perfluorinated alkyl group comprising 1-8 carbon atoms and optionally comprising at least one catenated O or N atom, or (ii) the two R.sub.f's are bonded together to form a ring structure optionally comprising at least one catenated O or N atom, wherein the ring of the ring structure consists of 5-7 atoms, no more than 10 carbon atoms, and is perfluorinated. The applications of the compound include solvent cleaning, electrolyte solvents or additives, heat transfer, and vapour phase soldering.

The present invention relates to an unsaturated fluorinated ether or amine compound of formula (I) with low global warming potential and method of making the compound (I), where R.sub.H.sup.1 is and R.sub.H.sup.2 are independently selected from H or CH.sub.3, wherein when R.sub.H.sup.1 is CH.sub.3 then R.sub.H.sup.2 is H and when R.sub.H.sup.2 is CH.sub.3, then R.sub.H.sup.1 is H; X is O or N and when X is O, then n is 1 and R.sub.f is a linear or branched perfluorinated alkyl group comprising 1-10 carbon atoms and optionally comprising at least one catenated O or N atom; X is N, then n is 2 and (i) each R.sub.f is independently selected from a linear or branched perfluorinated alkyl group comprising 1-8 carbon atoms and optionally comprising at least one catenated O or N atom, or (ii) the two R.sub.f's are bonded together to form a ring structure optionally comprising at least one catenated O or N atom, wherein the ring of the ring structure consists of 5-7 atoms, no more than 10 carbon atoms, and is perfluorinated. The applications of the compound include solvent cleaning, electrolyte solvents or additives, heat transfer, and vapour phase soldering.

The invention relates to improved method of synthesis for Treprostinil comprising condensation reaction of the carbonyl compound having allyl, alkyl, crotyl or MEM-protected phenolic hydroxyl group, compound (4) with a hydroxyl-protected alkynol (5) to give the condensation product, compound (6). Subjecting compound (6) to oxidation, reduction, hydroxyl protection and carbonylation, cyclization reactions gave the tricyclic derivative (10). Further reactions comprising reduction, hydrogenation and deprotection of the phenolic and side-chain hydroxyl groups, wherein the sequence and choice of reagents was governed by protecting groups, gave the triol intermediate, compound (14). Cyanoalkylation at phenolic hydroxyl functionality and further hydrolysis yielded the prostacyclin compound, Treprostinil (1) and its pharmaceutically acceptable salts, having desired purity.

The invention relates to improved method of synthesis for Treprostinil comprising condensation reaction of the carbonyl compound having allyl, alkyl, crotyl or MEM-protected phenolic hydroxyl group, compound (4) with a hydroxyl-protected alkynol (5) to give the condensation product, compound (6). Subjecting compound (6) to oxidation, reduction, hydroxyl protection and carbonylation, cyclization reactions gave the tricyclic derivative (10). Further reactions comprising reduction, hydrogenation and deprotection of the phenolic and side-chain hydroxyl groups, wherein the sequence and choice of reagents was governed by protecting groups, gave the triol intermediate, compound (14). Cyanoalkylation at phenolic hydroxyl functionality and further hydrolysis yielded the prostacyclin compound, Treprostinil (1) and its pharmaceutically acceptable salts, having desired purity.

The invention provides a new convergent approach for the synthesis of 2-fluoro-6-methylene-carbocyclic adenosine (FMCA) and 2-fluoro-6-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R,4R)-3-tert-butoxy-4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.