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, anydrate 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. ##STR00001##
Also disclosed are treprostinil intermediates and the preparation of the intermediates.

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, anydrate 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. ##STR00001##
Also disclosed are treprostinil intermediates and the preparation of the intermediates.

The present invention relates to a 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the following general formula (1): HOCH.sub.2CH.sub.2CH=CHCH.sub.2CH.sub.2OCH.sub.2OCH.sub.2R.sup.1 (1), R.sup.1 representing a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group; and also relates to a process for preparing a 3,13-octadecadien-1-ol compound of the following formula (6): CH.sub.3(CH.sub.2).sub.3CHCH(CH.sub.2).sub.8CH?CHCH.sub.2CH.sub.2OH (6) from the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1).

The present invention relates to a 6-hydroxy-3-hexenyl alkoxymethyl ether compound of the following general formula (1): HOCH.sub.2CH.sub.2CH=CHCH.sub.2CH.sub.2OCH.sub.2OCH.sub.2R.sup.1 (1), R.sup.1 representing a hydrogen atom, an n-alkyl group having 1 to 9 carbon atoms, or a phenyl group; and also relates to a process for preparing a 3,13-octadecadien-1-ol compound of the following formula (6): CH.sub.3(CH.sub.2).sub.3CHCH(CH.sub.2).sub.8CH?CHCH.sub.2CH.sub.2OH (6) from the 6-hydroxy-3-hexenyl alkoxymethyl ether compound (1).

Methods of producing a 2,4-dienal acetal compound and a 2,4-dienal compound useful as synthesis intermediates of a sex pheromone compound having a conjugated diene structure or a conjugated triene structure. More specifically, a method produces a 2,4-dienal acetal compound of Formula (2): R.sup.1CHCHCHCHCH(OR.sup.2)(OR.sup.3), including a step of subjecting a 2-enal acetal compound having a leaving group X at position C5 and being expressed by Formula (1): R.sup.1CHXCH.sub.2CHCHCH(OR.sup.2)(OR.sup.3) to an elimination reaction in the presence of a base to obtain the 2,4-dienal acetal compound (2); and a method for producing a 2,4-dienal compound of Formula (3): R.sup.1CHCHCHCHCHO, further including a step of deprotecting the 2,4-dienal acetal compound (2) to obtain the 2,4-dienal compound (3).

Methods of producing a 2,4-dienal acetal compound and a 2,4-dienal compound useful as synthesis intermediates of a sex pheromone compound having a conjugated diene structure or a conjugated triene structure. More specifically, a method produces a 2,4-dienal acetal compound of Formula (2): R.sup.1CHCHCHCHCH(OR.sup.2)(OR.sup.3), including a step of subjecting a 2-enal acetal compound having a leaving group X at position C5 and being expressed by Formula (1): R.sup.1CHXCH.sub.2CHCHCH(OR.sup.2)(OR.sup.3) to an elimination reaction in the presence of a base to obtain the 2,4-dienal acetal compound (2); and a method for producing a 2,4-dienal compound of Formula (3): R.sup.1CHCHCHCHCHO, further including a step of deprotecting the 2,4-dienal acetal compound (2) to obtain the 2,4-dienal compound (3).

Methods of producing a 2,4-dienal acetal compound and a 2,4-dienal compound useful as synthesis intermediates of a sex pheromone compound having a conjugated diene structure or a conjugated triene structure. More specifically, a method produces a 2,4-dienal acetal compound of Formula (2): R.sup.1CHCHCHCHCH(OR.sup.2)(OR.sup.3), including a step of subjecting a 2-enal acetal compound having a leaving group X at position C5 and being expressed by Formula (1): R.sup.1CHXCH.sub.2CHCHCH(OR.sup.2)(OR.sup.3) to an elimination reaction in the presence of a base to obtain the 2,4-dienal acetal compound (2); and a method for producing a 2,4-dienal compound of Formula (3): R.sup.1CHCHCHCHCHO, further including a step of deprotecting the 2,4-dienal acetal compound (2) to obtain the 2,4-dienal compound (3).

Methods of producing a 2,4-dienal acetal compound and a 2,4-dienal compound useful as synthesis intermediates of a sex pheromone compound having a conjugated diene structure or a conjugated triene structure. More specifically, a method produces a 2,4-dienal acetal compound of Formula (2): R.sup.1CHCHCHCHCH(OR.sup.2)(OR.sup.3), including a step of subjecting a 2-enal acetal compound having a leaving group X at position C5 and being expressed by Formula (1): R.sup.1CHXCH.sub.2CHCHCH(OR.sup.2)(OR.sup.3) to an elimination reaction in the presence of a base to obtain the 2,4-dienal acetal compound (2); and a method for producing a 2,4-dienal compound of Formula (3): R.sup.1CHCHCHCHCHO, further including a step of deprotecting the 2,4-dienal acetal compound (2) to obtain the 2,4-dienal compound (3).

The present invention primarily relates to the use of 3-(4-isobutyl-2-methyl-cyclohexyl)pro-panal, 3-(4-Isobutyl-6-methyl-cyclohexa-1,5-dien-1-yl)propanal, 3-(4-isobutyl-6-meth-ylene-cyclohexen-1-yl)propanal, or 3-(4-isobutyl-6-methyl-cyclohexen-1-yl)propanal as perfuming ingredients. Moreover, the present invention relates to perfume compositions and perfumed products comprising the before mentioned perfuming ingredients. Still more particularly, the invention relates to a method for producing said perfumed products and a method of imparting and/or increasing i) floral and/or ii) green and/or iii) lily of the valley odor characteristics to perfumed products. This invention also relates to 3-(4-isobutyl-2-methyl-cyclohexyl)propanal, 3-(4-Isobutyl-6-methyl-cyclohexa-1,5-dien-1-yl)propanal, 3-(4-isobutyl-6-methylene-cyclohexen-1-yl)propanal, or 3-(4-isobutyl-6-methyl-cyclohexen-yl)propanal and a process for the preparation of said compounds.

The present invention primarily relates to the use of 3-(4-isobutyl-2-methyl-cyclohexyl)pro-panal, 3-(4-Isobutyl-6-methyl-cyclohexa-1,5-dien-1-yl)propanal, 3-(4-isobutyl-6-meth-ylene-cyclohexen-1-yl)propanal, or 3-(4-isobutyl-6-methyl-cyclohexen-1-yl)propanal as perfuming ingredients. Moreover, the present invention relates to perfume compositions and perfumed products comprising the before mentioned perfuming ingredients. Still more particularly, the invention relates to a method for producing said perfumed products and a method of imparting and/or increasing i) floral and/or ii) green and/or iii) lily of the valley odor characteristics to perfumed products. This invention also relates to 3-(4-isobutyl-2-methyl-cyclohexyl)propanal, 3-(4-Isobutyl-6-methyl-cyclohexa-1,5-dien-1-yl)propanal, 3-(4-isobutyl-6-methylene-cyclohexen-1-yl)propanal, or 3-(4-isobutyl-6-methyl-cyclohexen-yl)propanal and a process for the preparation of said compounds.