1. Process for the preparation of the pharmaceutically applicable polymorph Form I of (S)-(+)-methyl-\u03b1-(2-chlorophenyl)-6,7-dyhidro-thieno3,2-4-pyridine-5(4H)-acetate hydrogen sulfate of formula I
by reacting (S)-(+)-methyl-\u03b1-(2-chlorophenyl)-6,7-dyhidro-thieno3,2-cpyridine-5(4H)-acetate and sulfuric acid in the presence of solvents, the process comprising the steps of:
dissolving (S)-(+)-methyl-\u03b1-(2-chlorophenyl)-6,7-dyhidro-thieno3,2-cpyridine-5(4H)-acetate in an ether;
mixing this solution with a solution of a C6-C11 alcohol and sulfuric acid; and
recovering the so obtained compound of formula I from the mother liquor.
2. The process according to claim 1, wherein one or more straight or branched chain aliphatic ether of general formula Cn\u2014O\u2014Cm is used wherein n and m may be different or identical and n is 1-4 and m is 2-4.
3. The process according to claim 2, wherein methyl-t-butyl ether is used.
4. The process according to any one of claims 1-3, wherein one or more linear or branched, aliphatic or cyclic, primary, secondary or tertiary C6-C11 alcohol is used.
5. The process according to claim 4, wherein 1-decanol is used.
6. The process according to claim 1 wherein the (S)-(+)-methyl-\u03b1-(2-chlorophenyl)-6,7-dihydrothieno3,2-cpyridine-5(4H)-acetate is dissolved in 0.7-7.4fold amount of ether.
7. The process according to claim 6, wherein the (S)-(\xb1)-methyl-\u03b1-(2-chlorophenyl)-6,7-dihydrothieno3,2-cpyridine-5(4H)-acetate is dissolved in 7.4fold amount of ether.
8. The process according to any one of claims 1-7, wherein the alcohol is used in a 0.8-4.1fold amount based on the weight of the (S)-(+)-methyl-\u03b1-(2-chlorophenyl)-6,7-dihydrothieno3,2-cpyridine-5(4H)-acetate.
9. The process according to claim 8, wherein the alcohol is used in an 1.66fold amount based on the weight of (S)-(+)-methyl-\u03b1-(2-chlorophenyl)-6,7-dihydrothieno3,2-cpyridine-5(4H)-acetate.
10. The process according toy claim 1 wherein the ether is used in a 0.17-8.96fold amount based on the amount of the alcohol.
11. The process according to claim 10, wherein the ether is used in a 4.45fold amount based on the amount of the alcohol.
12. The process according to claim 1 wherein 0.9-1.25 mol equivalents sulfuric acid is used per one mol of (S)-(+)-methyl-\u03b1-(2-chlorophenyl)-6,7-dihydrothieno3,2*cpyridine-5(4H)-acetate.
13. The process according to claim 12, wherein 1 mol equivalent of sulfuric acid is used per one mol of (S)-(+)-methyl-\u03b1-(2-chlorophenyl)-6,7-dihydrothieno3,2-cpyridine5(4H)-acetate.
14. The process according to claim 1 wherein the sulfuric acid is employed in a concentration of 90-100 wt%.
15. The process according to claim 14, wherein the sulfuric acid is employed in a concentration of 96 wt%.
16. The process according to claim 1 wherein the crystallization is carried out for 24-48 hours.
17. The process according to claim 1 wherein the reaction is carried out at room temperature.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A water-in-oil emulsion composition, comprising:
(A) a solvent selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, ethers, glycol ethers, hydrofluoroethers, esters, ketones, aldehydes, lactones, terpenes, chlorinated non-polymeric hydrocarbons, pyrrolidones, and mixtures of two or more thereof;
(B) water; and
(C) a surfactant comprising:
(C)(i) a product made from the reaction of an acylating agent with ammonia, an amine, a hydroxyamine, an alcohol, water, or a mixture of two or more thereof;
(C)(ii) a product derived from: a polycarboxylic acylating agent; a copolymer derived from at least one olefin monomer and at least one alpha, beta unsaturated carboxylic acid or derivative thereof; and a linking compound having two or more primary amino groups, two or more secondary amino groups, at least one primary amino group and at least one secondary amino group, at least two hydroxyl groups, or at least one primary or secondary amino group and at least one hydroxyl group;
(C)(iii) a Mannich reaction product derived from a hydroxy aromatic compound, an aldehyde or a ketone, and an amine containing at least one primary or secondary amino group;
(C)(iv) a hydrocarbyl substituted carboxylic acid, the hydrocarbyl substiuent of the acid containing at least about 12 carbon atoms;
(C)(v) at least one compound represented by one or more of the formulae:
13
14
wherein in Formulae (C)(v)-1 to (C)(v)-6, each R is independently hydrogen or a hydrocarbyl group of up to about 60 carbon atoms; each R and R is independently an alkylene group of 1 to about 20 carbon atoms; each R is independently hydrogen, or an acyl or hydrocarbyl group of up to about 30 carbon atoms; n is a number in the range of zero to about 50; and x, y and z are independently numbers in the range of zero to about 50 with the total for x, y and z being at least 1;
(C)(vi) an ionic or a nonionic compound having a hydrophilic-lipophilic balance of about 1 to about 40; or
(C)(vii) a mixture of two or more of (C)(i) through (C)(vi);
the composition being characterized by the absence of an oxygen supplying oxidizer salt wherein (A) is an aliphatic hydrocarbon, aromatic hydrocarbon, alcohol or ether.
2. The composition of claim 1 wherein the composition further comprises a rheology control agent, an inorganic base, an inorganic salt, an antimisting agent, odor suppressant, corrosion inhibitor, coloring agent, antifreeze agent, biocide, or mixture of two or more thereof.
3. The composition of claim 1 wherein (A) is selected from the group consisting of: naphtha; mineral spirits; turpentine; toluene; xylene; methylene chloride; perchloroethylene; acetone; methyl ethyl ketone; N-methyl pyrrolidone; dimethyl glutarate; dimethyl adipate; and mixtures of two or more thereof.
4. The composition of claim 1 wherein the surfactant (C)(i) is the product made by reacting a fatty acid with an alkanol amine.
5. The composition of claim 1 wherein the surfactant (C)(i) is the product made by the reaction of a polyisobutene substituted succinic acid or anhydride with an alkanol amine.
6. The composition of claim 1 wherein the surfactant (C)(i) is the product made by the reaction of a polyisobutene substituted succinic acid or anhydride with an alkanol amine, the polyisobutene substituted succinic acid or anhydride being characterized by an average of at least about 1.3 succinic groups for each equivalent weight of the polyisobutene substitutent.
7. The composition of claim 1 wherein surfactant (C)(i) comprises a mixture of: the reaction product of a fatty acid with an alkanol amine; and the reaction product of a polyisobutene substituted succinic acid or anhydride with an alkanol amine or an alkylene polyamine, the polyisobutene substituent having a number average molecular weight of about 750 to about 3000.
8. The composition of claim 1 wherein surfactant (C)(i) comprises a mixture of: the product made from the reaction of a polyisobutene-substituted succinic acid or anhydride with an alkanol amine wherein the polyisobutene group has a number average molecular weight of about 1500 to about 3000; the product made from the reaction of a hydrocarbon-substituted succinic acid or anhydride with an alkanol amine wherein the hydrocarbon substituent has about 12 to about 30 carbon atoms; and the product made from the reaction of a polyisobutene-substituted succinic acid or anhydride with at least one alkylene polyamine wherein the polyisobutene group has a number average molecular weight of about 750 to about 1500.
9. The composition of claim 1 wherein surfactant (C)(i) comprises (I) a first polycarboxylic acylating agent having at least one hydrocarbon substituent of about 6 to about 500 carbon atoms, (II) a second polycarboxylic acylating agent optionally having at least one hydrocarbon substituent of up to about 500 carbon atoms, the polycarboxylic acylating agents (I) and (II) being the same or different and being linked together by (III) a linking group derived from a compound having two or more primary amino groups, two or more secondary amino groups, at least one primary amino group and at least one secondary amino group, at least two hydroxyl groups, or at least one primary or secondary amino group and at least one hydroxyl group, the polycarboxylic acylating agents (I) and (II) being reacted with ammonia, an amine, a hydroxyamine, an alcohol, water, or a mixture of two or more thereof.
10. The composition of claim 1 wherein the surfactant (C)(ii) is comprised of a polyisobutene-substituted succinic anhydride and a copolymer derived from an alpha-olefin and maleic anhydride, the anhydride and the copolymer being linked together by an ethylene polyamine.
11. The composition of claim 1 wherein the surfactant (C)(iii) is a Mannich reaction product derived from:
(C)(iii)(1) a hydroxy aromatic compound having the formula
15
wherein in Formula (C)(iii)-1: Ar is an aromatic group; m is 1, 2 or 3; n is a number from 1 to about 4; with the proviso that the sum of m and n is up to the number of available positions on Ar that can be substituted; each R1 independently is a hydrocarbon group of up to about 400 carbon atoms; and R2 is H, amino or carboxyl;
(C)(iii)(2) an aldehyde or ketone having the formula
16
or a precursor thereof; wherein in Formula (C)(iii)-2: R1 and R2 independently are H or hydrocarbon groups having from 1 to about 18 carbon atoms; and R2 can also be a carbonyl-containing hydrocarbon group having from 1 to about 18 carbon atoms; and
(C)(iii)(3) an amine containing at least one primary or secondary amino group.
12. The composition of claim 1 wherein the hydrocarbyl substituent for the surfactant (C)(iv) is derived from polyisobutene, polypropylene, polyethylene, a copolymer derived from isobutene and butadiene, or a copolymer derived from isobutene and isoprene.
13. The composition of claim 1 wherein the surfactant (C)(iv) comprises a polyisobutene substituted succinic acid.
14. The composition of claim 1 wherein (C)(v) comprises a C9-C11 alkoxy poly (ethoxy)8 alcohol; C12-C15 alkoxy poly (isopropoxy)22-26 alcohol; oleyl alcohol pentaethoxylate; diglycerol monooleate; diglycerol monostearate; polyglycerol monooleate; polyethylene glycol distearate; polyethylene glycol dioleate; polyethylene glycol soya bean oil ester; glycerol monooleate; diglycerol dioleate; diglycerol distearate; polyglycerol dioleate; sorbitan monooleate; sorbitan monoisostearate; sorbitan sesquioleate; sorbitan trioleate; polyethoxy glycerol trioleate; or a mixture of two or more thereof.
15. The composition of claim 1 wherein the surfactant (C)(vi) comprises an alkylaryl sulfonate, amine oxide, carboxylated alcohol ethoxylate, ethoxylated amine, ethoxylated amide, glycerol ester, glycol ester, imidazoline derivative, lecithin, lecithin derivative, lignin, lignin derivative, monoglyceride, monoglyceride derivative, olefin sulfonate, phosphate ester, phosphate ester derivative, propoxylated fatty acid, ethoxylated fatty acid, propoxylated alcohol or alkyl phenol, sucrose ester, sulfonate of dodecyl or tridecyl benzene, naphthalene sulfonate, petroleum sulfonate, tridecyl or dodecyl benzene sulfonic acid, sulfosuccinate, sulfosuccinate derivative, or mixture of two or more thereof, each of these compounds having a hydrocarbon group of at least about 8 carbon atoms.
16. The composition of claim 2 wherein the rheology control agent comprises: a polyisobutene; a polyacrylate; a polymethacrylate; an ethylene-propylene copolymer; a terpolymer derived from ethylene, propylene and a non-conjugated diene; an ester derived from a copolymer of styrene and maleic anhydride, and an alcohol of up to about 18 carbon atoms; a hydrogenated copolymer derived from styrene and a conjugated diene; an ethylenepropylenenon-conjugated diene terpolymer with a functionalized monomer grafted onto the backbone of the terpolymer; an ethylenepropylenenorbornadiene terpolymer with maleic anhydride grafted onto the backbone of the terpolymer; an organically modified clay; diatomaceous earth; kaolin; vaterite; a gelled overbased sulfonate; a gelled overbased carboxylate, or a mixture of two or more thereof.
17. A water-in-oil emulsion composition, comprising:
from about 25% to about 85% by weight of a solvent selected from the group consisting of: naphtha; mineral spirits; turpentine; toluene; xylene; methylene chloride; perchloroethylene; acetone; methyl ethyl ketone; and mixtures of two or more thereof;
from about 15% to about 75% by weight water; and
the reaction product of a hydrocarbon substituted succinic acid or anhydride with an alkanol amine;
the composition being characterized by the absence of an oxygen supplying oxidizer salt.
18. A water-in-oil emulsion composition, comprising:
(A) a solvent selected from the group consisting of glycol ethers, hydrofluoroethers, esters, ketones, aldehydes, lactones, terpenes, chlorinated non-polymeric hydrocarbons, pyrrolidones, and mixtures of two or more thereof;
(B) water; and
(C) a surfactant comprising:
(C)(i) a product made from the reaction of an acylating agent with ammonia, an amine, a hydroxyamine, an alcohol, water, or a mixture of two or more thereof;
(C)(ii) a product derived from: a polycarboxylic acylating agent; a copolymer derived from at least one olefin monomer and at least one alpha, beta unsaturated carboxylic acid or derivative thereof; and a linking compound having two or more primary amino groups, two or more secondary amino groups, at least one primary amino group and at least one secondary amino group, at least two hydroxyl groups, or at least one primary or secondary amino group and at least one hydroxyl group;
(C)(iii) a Mannich reaction product derived from a hydroxy aromatic compound, an aldehyde or a ketone, and an amine containing at least one primary or secondary amino group;
(C)(iv) a hydrocarbyl substituted carboxylic acid, the hydrocarbyl substiuent of the acid containing at least about 12 carbon atoms;
(C)(v) at least one compound represented by one or more of the formulae:
17
18
wherein in Formulae (C)(v)-1 to (C)(v)-6, each R is independently hydrogen or a hydrocarbyl group of up to about 60 carbon atoms; each R and R is independently an alkylene group of 1 to about 20 carbon atoms; each R is independently hydrogen, or an acyl or hydrocarbyl group of up to about 30 carbon atoms; n is a number in the range of zero to about 50; and x, y and z are independently numbers in the range of zero to about 50 with the total for x, y and z being at least 1;
(C)(vi) an ionic or a nonionic compound having a hydrophilic-lipophilic balance of about 1 to about 40; or
(C)(vii) a mixture of two or more of (C)(i) through (C)(vi).
19. A water-in-oil emulsion composition, comprising:
(A) a solvent selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, ethers, glycol ethers, hydrofluoroethers, esters, ketones, aldehydes, lactones, terpenes, chlorinated non-polymeric hydrocarbons, pyrrolidones, and mixtures of two or more thereof;
(B) water;
(C) a surfactant comprising:
(C)(i) a product made from the reaction of an acylating agent with ammonia, an amine, a hydroxyamine, an alcohol, water, or a mixture of two or more thereof;
(C)(ii) a product derived from: a polycarboxylic acylating agent; a copolymer derived from at least one olefin monomer and at least one alpha, beta unsaturated carboxylic acid or derivative thereof; and a linking compound having two or more primary amino groups, two or more secondary amino groups, at least one primary amino group and at least one secondary amino group, at least two hydroxyl groups, or at least one primary or secondary amino group and at least one hydroxyl group;
(C)(iii) a Mannich reaction product derived from a hydroxy aromatic compound, an aldehyde or a ketone, and an amine containing at least one primary or secondary amino group;
(C)(iv) a hydrocarbyl substituted carboxylic acid, the hydrocarbyl substiuent of the acid containing at least about 12 carbon atoms;
(C)(v) at least one compound represented by one or more of the formulae:
19
20
wherein in Formulae (C)(v)-1 to (C)(v)-6, each R is independently hydrogen or a hydrocarbyl group of up to about 60 carbon atoms; each R and R is independently an alkylene group of 1 to about 20 carbon atoms; each R is independently hydrogen, or an acyl or hydrocarbyl group of up to about 30 carbon atoms; n is a number in the range of zero to about 50; and x, y and z are independently numbers in the range of zero to about 50 with the total for x, y and z being at least 1;
(C)(vi) an ionic or a nonionic compound having a hydrophilic-lipophilic balance of about 1 to about 40; or
(C)(vii) a mixture of two or more of (C)(i) through (C)(vi); and
(D) a rheology control agent selected from a polyisobutene; a polyacrylate; a polymethacrylate; an ethylene-propylene copolymer; a terpolymer derived from ethylene, propylene and a non-conjugated diene; an ester derived from a copolymer of styrene and maleic anhydride, and an alcohol of up to about 18 carbon atoms; a hydrogenated copolymer derived from styrene and a conjugated diene; an ethylenepropylenenon-conjugated diene terpolymer with a functionalized monomer grafted onto the backbone of the terpolymer; an ethylenepropylenenorbornadiene terpolymer with maleic anhydride grafted onto the backbone of the terpolymer; an organically modified clay; diatomaceous earth; kaolin; vaterite; a gelled overbased sulfonate; a gelled overbased carboxylate, or a mixture of two or more thereof.
20. A process for removing a non-aqueous coating, wax or grease from a substrate, the process comprising applying a water-in-oil emulsion composition to the non-aqueous coating, wax or grease, and removing the applied water-in-oil composition and non-aqueous coating, wax or grease from the substrate, the water-in-oil emulsion composition comprising:
(A) a solvent selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, ethers, glycol ethers, hydrofluoroethers, esters, ketones, aldehydes, lactones, terpenes, chlorinated non-polymeric hydrocarbons, pyrrolidones, and mixtures of two or more thereof;
(B) water; and
(C) a surfactant comprising:
(C)(i) a product made from the reaction of an acylating agent with ammonia, an amine, a hydroxyamine, an alcohol, water, or a mixture of two or more thereof;
(C)(ii) a product derived from: a polycarboxylic acylating agent; a copolymer derived from at least one olefin monomer and at least one alpha, beta unsaturated carboxylic acid or derivative thereof; and a linking compound having two or more primary amino groups, two or more secondary amino groups, at least one primary amino group and at least one secondary amino group, at least two hydroxyl groups, or at least one primary or secondary amino group and at least one hydroxyl group;
(C)(iii) a Mannich reaction product derived from a hydroxy aromatic compound, an aldehyde or a ketone, and an amine containing at least one primary or secondary amino group;
(C)(iv) a hydrocarbyl substituted carboxylic acid, the hydrocarbyl substiuent of the acid containing at least about 12 carbon atoms;
(C)(v) at least one compound represented by one or more of the formulae:
21
22
wherein in Formulae (C)(v)-1 to (C)(v)-6, each R is independently hydrogen or a hydrocarbyl group of up to about 60 carbon atoms; each R and R is independently an alkylene group of 1 to about 20 carbon atoms; each R is independently hydrogen, or an acyl or hydrocarbyl group of up to about 30 carbon atoms; n is a number in the range of zero to about 50; and x, y and z are independently numbers in the range of zero to about 50 with the total for x, y and z being at least 1;
(C)(vi) an ionic or a nonionic compound having a hydrophilic-lipophilic balance of about 1 to about 40; or
(C)(vii) a mixture of two or more of (C)(i) through (C)(vi).