Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anhydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates. ##STR00001##

Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anhydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates. ##STR00001##

Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anhydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates. ##STR00001##

A process for preparing 4-penten-2-ynal of the following formula (2):
CH.sub.2═CHC≡CCHO  (2)
the process comprising a step of hydrolyzing a 5,5-dialkoxy-1-penten-3-yne compound of the following general formula (1):
CH.sub.2═CHC≡CCH(OR.sup.1)(OR.sup.2)  (1)
wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 8, more preferably 1 to 4, or R.sup.1 and R.sup.2 may be bonded to each other to form a divalent hydrocarbon group, R.sup.1-R.sup.2, having from 2 to 10 carbon atoms,
to obtain 4-penten-2-ynal (2). ##STR00001##

A process for preparing 4-penten-2-ynal of the following formula (2):
CH.sub.2═CHC≡CCHO  (2)
the process comprising a step of hydrolyzing a 5,5-dialkoxy-1-penten-3-yne compound of the following general formula (1):
CH.sub.2═CHC≡CCH(OR.sup.1)(OR.sup.2)  (1)
wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 8, more preferably 1 to 4, or R.sup.1 and R.sup.2 may be bonded to each other to form a divalent hydrocarbon group, R.sup.1-R.sup.2, having from 2 to 10 carbon atoms,
to obtain 4-penten-2-ynal (2). ##STR00001##

The present invention provide for preparing a formylalkenyl alkoxymethyl ether compound of the following general formula (2): R.sup.3CH.sub.2OCH.sub.2O(CH.sub.2).sub.aCH═CHCHO (2), wherein R.sup.3 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group; and “a” represents an integer of 1 to 10, the process comprising: hydrolyzing a dialkoxyalkenyl alkoxymethyl ether compound of the following general formula (1): R.sup.3CH.sub.2OCH.sub.2O(CH.sub.2).sub.aCH═CHCH(OR.sup.1)(OR.sup.2) (1), wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 15 carbon atoms, or R.sup.1 and R.sup.2 may form together a divalent hydrocarbon group, R.sup.1-R.sup.2, having 2 to 10 carbon atoms; and R.sup.3 and “a” are as defined above, in the presence of an acid while removing an alcohol compound thus generated to form the formylalkenyl alkoxymethyl ether compound (2).

The present invention provide for preparing a formylalkenyl alkoxymethyl ether compound of the following general formula (2): R.sup.3CH.sub.2OCH.sub.2O(CH.sub.2).sub.aCH═CHCHO (2), wherein R.sup.3 represents a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group; and “a” represents an integer of 1 to 10, the process comprising: hydrolyzing a dialkoxyalkenyl alkoxymethyl ether compound of the following general formula (1): R.sup.3CH.sub.2OCH.sub.2O(CH.sub.2).sub.aCH═CHCH(OR.sup.1)(OR.sup.2) (1), wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 15 carbon atoms, or R.sup.1 and R.sup.2 may form together a divalent hydrocarbon group, R.sup.1-R.sup.2, having 2 to 10 carbon atoms; and R.sup.3 and “a” are as defined above, in the presence of an acid while removing an alcohol compound thus generated to form the formylalkenyl alkoxymethyl ether compound (2).

The present invention discloses a cobalt compound of formula (I), a process for the preparation and use thereof. The present invention further relates to a pharmaceutical composition and a method inhibition of Tau Aggregation in a subject in need thereof using compound of formula (I). ##STR00001##

The present invention discloses a cobalt compound of formula (I), a process for the preparation and use thereof. The present invention further relates to a pharmaceutical composition and a method inhibition of Tau Aggregation in a subject in need thereof using compound of formula (I). ##STR00001##

The present invention provides a production method of α-fluoroacrylate ester, a composition containing a highly-pure fluorocyclopropane derivative and a composition containing highly-pure α-fluoroacrylate ester. The present invention relates to a method of producing a compound represented by the following formula (F), including subjecting a composition containing a compound represented by the following formula (A) to a purification treatment in the order of distillation and washing with an aqueous alkali solution to give a purified product containing a compound represented by the following formula (A), and subjecting the purified product to a thermal decomposition reaction, a composition containing a highly-pure compound represented by the following formula (A), and a composition containing a highly-pure compound represented by the following formula (F), wherein R may be the same or different and is a monovalent hydrocarbon group, and X is a halogen atom: ##STR00001##