DK167062B1 - METHOD FOR PREPARING 1,4-BIS (2,2,2-TRIFLUORETHOXY) BENZEN - Google Patents
METHOD FOR PREPARING 1,4-BIS (2,2,2-TRIFLUORETHOXY) BENZEN Download PDFInfo
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- DK167062B1 DK167062B1 DK112180A DK112180A DK167062B1 DK 167062 B1 DK167062 B1 DK 167062B1 DK 112180 A DK112180 A DK 112180A DK 112180 A DK112180 A DK 112180A DK 167062 B1 DK167062 B1 DK 167062B1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/46—Friedel-Crafts reactions
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
Description
i DK 167062 B1in DK 167062 B1
Den foreliggende opfindelse angår en særlig fremgangsmåde til fremstilling af forbindelsen 1,4-bis(2,2,2-trifluor-ethoxy)benzen.The present invention relates to a particular process for the preparation of the compound 1,4-bis (2,2,2-trifluoroethoxy) benzene.
5 Det er fra GB patentskrift nr. 1 143 481 og US patentskrift nr. 3 719 687 kendt at fremstille lignende forbindelser under anvendelse af fluorholdige sulfonater. Det har nu overraskende vist sig, at l,4-bis(2,2,2-trifluor-ethoxy)benzen kan fremstilles i bedre udbytte ved fremit) gangsmåden ifølge opfindelsen, ved hvilken man omsætter 1.4- dibrombenzen med et alkyleringsmiddel med formlen CF^CHUjO-A, hvor A er et alkalimetal, i nærværelse af cupro- eller cupriioner i et stærkt polært opløsningsmiddel.It is known from GB Patent No. 1,143,481 and US Patent No. 3,719,687 to prepare similar compounds using fluorine-containing sulfonates. It has now surprisingly been found that 1,4-bis (2,2,2-trifluoroethoxy) benzene can be produced in better yield by the process of the invention, by reacting 1,4-dibromobenzene with an alkylating agent of formula CF Wherein CH is an alkali metal in the presence of cuprous or cuprous ions in a highly polar solvent.
15 1.4- Bis(2,2,2-trifluorethoxy)benzen, der er kendt fra US patent nr. 4 071 524, er velegnet til brug ved fremstilling af det kendte antiarrhytmiske middel 2,5-bis(2,2,2-trifluorethoxy)-N-(2-piperidylmethyl)benzamid (flecainid) 20 og salte deraf ud fra brom- eller hydroxylsubstituerede benzener.1.4- Bis (2,2,2-trifluoroethoxy) benzene, known from U.S. Patent No. 4,071,524, is suitable for use in the preparation of the known antiarrhythmic agent 2,5-bis (2,2,2- trifluoroethoxy) -N- (2-piperidylmethyl) benzamide (flecainide) and salts thereof from bromo- or hydroxyl-substituted benzenes.
Den antiarrhytmiske forbindelse, flecainid, dens salte og en fremgangsmåde til fremstilling deraf er beskrevet i US 25 patentskrift nr. 3 900 481. Den har følgende formel CF3CH2°^gj-C-N-CH2—CnJ VI11 'SVxoch2cf3The antiarrhythmic compound, flecainide, its salts and a process for its preparation are disclosed in U.S. Patent No. 3,900,481. It has the following formula CF3CH2 ° Cg-C-N-CH2-CnJ VI11 'SVxoch2cf3
Flecainid kan også fremstilles som beskrevet i det føl-35 gende ud fra 1,4-dibrombenzen. En sådan fremgangsmåde er at foretrække frem for den kendte fremgangsmåde på grund af forskellige praktiske fordele, f.eks. de relativt lave DK 167062 B1 2 omkostninger for udgangsmaterialerne, den lette udøvelse af de deri indgående enhedsoperationer og de forholdsvis høje udbytter af det ønskede produkt.Flecainide can also be prepared as described below from 1,4-dibromobenzene. Such a method is preferable to the known method because of various practical advantages, e.g. the relatively low cost of the starting materials, the ease of carrying out the unit operations included therein and the relatively high yields of the desired product.
55
Denne fremgangsmåde omfatter følgende trin, hvor første trin er fremgangsmåden ifølge opfindelsen.This process comprises the following steps, the first step being the method of the invention.
(1) Omsætning af en forbindelse med formlen 10(1) Reaction of a compound of formula 10
Brbr
XX
Br 15 med et hensigtsmæssigt alkyleringsmiddel med formlen cf3ch2o-a 20 hvori A er et alkalimetal til opnåelse af forbindelsen med formlenBr 15 with a suitable alkylating agent of the formula cf3ch2o-a20 wherein A is an alkali metal to give the compound of the formula
25 CFCHO25 CFCHO
XX
OCH2CF3 30 (2) acetylering i nærværelse af en Lewis-syrekataly sator til opnåelse af en substitueret acetophe-non med formlen 0OCH2CF3 (2) acetylation in the presence of a Lewis acid catalyst to give a substituted acetopheone of formula 0
IIII
35 CF3CH2°x^/CCH3 {XT 111 OCHjCF, DK 167062 B1 3 (3) enten (a) chlorering af den substituerede acetophenon til dannelse af den tilsvarende α,α-dichlor- 5 acetophenon med formlen 9 ' iv CF-CH 0 CCHC1 3 2 C12 XOCH2CF3 (b) tilsætning af en pufrende base og yderligere chlorering til opnåelse af den tilsvarende 15 o,a,o,-trichloracetophenon med formlen 0CF3CH2 ° x ^ / CCH3 {XT 111 OCHjCF, DK 167062 B1 3 (3) either (a) chlorination of the substituted acetophenone to give the corresponding α, α-dichloro-acetophenone of formula 9 'iv CF-CH CCHC1 3 2 C12 XOCH2CF3 (b) adding a buffer base and further chlorination to give the corresponding 15 o, a, o, -trichloroacetophenone of formula 0
t Vt V
CF,CH,0 CCC1,CF, CH, 0 CCC1,
XX
xoch2cf3 eller 25 (c) omsætning af den substituerede acetophenon med hypochlorit til dannelse af den tilsvarende benzoesyre med formlen 0xoch2cf3 or (c) reacting the substituted acetophenone with hypochlorite to give the corresponding benzoic acid of formula 0
30 CF CH O JL30 CF CH O JL
3 2 VI3 2 VI
XX
xoch2cf3 og 35 DK 167062 B1 4 (d) omsætning af syren med et uorganiske syre-chlorid til opnåelse af syrechloridet med formlen 0xoch2cf3 and 35 (d) reacting the acid with an inorganic acid chloride to give the acid chloride of formula 0
5 IIII
CF3CH2°X-/CC1 VIICF3CH2 ° X- / CC1 VII
vOCH2CF3 og derpå 10 (4) omsætning af produktet fra trin 3(b) eller trin 3(d) enten med 2-(aminomethyl)piperidin 15 til dannelse af det ønskede produkt i ét trin eller med 2-(aminomethyl)pyridin 20 efterfulgt af reduktion til dannelse af det tønskede produkt, som fri base eller eventuelt i form af acetatsaltet deraf.vOCH2CF3 and then 10 (4) reacting the product of step 3 (b) or step 3 (d) either with 2- (aminomethyl) piperidine 15 to give the desired product in one step or with 2- (aminomethyl) pyridine 20 followed by of reduction to form the desired product as free base or optionally in the form of the acetate salt thereof.
25 30 35 DK 167062 B1 525 30 35 DK 167062 B1 5
Totalprocessen følger reaktionsskemaet:The overall process follows the reaction scheme:
OISLAND
I! 5 Br OCH CF0 CF-CHLO ^CCH_ (¾ — ro) -- Yof '—, (i) (2)IN! 5 Br AND CF0 CF-CHLO ^ CCH_ (¾ - ro) - Yof '-, (i) (2)
Br I II OCH2CF3 111 OCH2CF3 10 (3)(a) 0 V ° (3) (c) |1 li CFoCH_0 CCC10 CF,CH O CCHCl- .. ’ ^ ^ ^ v 'NsOCH2CF3 iv X'och2cf3 (4) 20 o o il i!Br I II OCH2CF3 111 OCH2CF3 10 (3) (a) 0 V ° (3) (c) | 1 li CFoCH_0 CCC10 CF, CH O CCHCl- .. '^ ^ v' NsOCH2CF3 iv X'och2cf3 (4) 20 oo il i!
— CF.,CKL O CC1 CF,CrL,0 COH- CF., CKL O CC1 CF, CrL, 0 COH
Λ§( -J§ (-J
25 vil xoch2cf3 VI xoch2cf3 l-f VIII -?* 30 35 DK 167062 Bl 6 1,4-Dibrombenzen I omsættes hensigtsmæssigt med 2,2,2-trifluorethoxidionen i en stærk polær opløsningsmiddel-blanding ved en temperatur på op til tilbagesvalingstemperaturen for opløsningen i nærværelse af cupro- eller 5 cupriioner til opnåelse af det ønskede produkt II i godt udbytte. 2,2,2-trifluorethoxid opnås fra den tilsvarende alkohol ved omsætning med en stærk base, såsom natriumhydroxid eller foretrukkent natriumhydrid. Egnede opløsningsmiddelblandinger omfatter dimethylsulfoxid, N,N-di-10 methylacetamid og foretrukkent Ν,Ν-dimethylformamid, hver med ca. 10 til 50%, og foretrukkent ca. 20%, 2,2,2-tri-fluorethanol. Cuproionen tilvejebringes f.eks. ved hjælp af et cuprohalogenid, såsom cuproiodid eller cuprobromid. Cupriionen tilvejebringes f.eks. med cupribromid, cupri-15 sulfat eller cupriacetat.25, xoch2cf3 VI xoch2cf3 lf VIII -? * 30 35 DK 167062 B1 6 1,4-Dibromobenzene I is suitably reacted with the 2,2,2-trifluoroethoxide ion in a strong polar solvent mixture at a temperature up to the reflux temperature of the solution in the presence of cupro or 5 cup rions to obtain the desired product II in good yield. 2,2,2-trifluoroethoxide is obtained from the corresponding alcohol by reaction with a strong base such as sodium hydroxide or preferred sodium hydride. Suitable solvent mixtures include dimethyl sulfoxide, N, N-dimethylacetamide and preferably Ν, Ν-dimethylformamide, each having about 10 to 50%, and preferably about 10%. 20%, 2,2,2-trifluoroethanol. The cup rion is provided e.g. by a cuprohalide such as cuproiodide or cuprobromide. The cup rion is provided e.g. with cupri bromide, cupri sulphate or cupri acetate.
Det efterfølgende eksempel forklarer fremgangsmåden iføl ge opfindelsen nærmere.The following example further explains the method of the invention.
20 EKSEMPEL 1 A = NaEXAMPLE 1 A = Na
Til 0,20 mol (9,6 g) 50%'s natriumhydrid i 40 ml N,N-di-25 methylformamid sættes 40 ml 2,2,2-trifluorethanol efterfulgt af 0,034 mol (8,0 g) 1,4-dibrombenzen og 0,006 mol (1,0 g) cuproiodid. Blandingen opvarmes ved tilbagesvalingstemperaturen i 4 timer, afkøles derpå til ca. 25 °C og filtreres. Resten vaskes med Ν,Ν-dimethylformamid. Op-30 løsningen udhældes derpå i vand, og bundfaldet fraskilles ved filtrering. Produktet opløses i diethylether og filtreres, og filtratopløsningen inddampes til opnåelse af en fast rest, som vaskes med hexan og tørres. Produktet er 7,3 g (80%) 1,4-bis(2,2,2-trifluorethoxy)benzen, smp.To 0.20 mole (9.6 g) of 50% sodium hydride in 40 ml of N, N-dimethylformamide is added 40 ml of 2,2,2-trifluoroethanol followed by 0.034 mol (8.0 g) 1.4 -dibromobenzene and 0.006 mole (1.0 g) of cuprous iodide. The mixture is heated at reflux temperature for 4 hours, then cooled to ca. 25 ° C and filtered. The residue is washed with Ν, Ν-dimethylformamide. The solution is then poured into water and the precipitate is separated by filtration. The product is dissolved in diethyl ether and filtered and the filtrate solution is evaporated to give a solid residue which is washed with hexane and dried. The product is 7.3 g (80%) of 1,4-bis (2,2,2-trifluoroethoxy) benzene, m.p.
35 77 til 79 °C.35 to 79 ° C.
DK 167062 B1 7DK 167062 B1 7
Omsætningen gentages derpå som følger, idet man varierer betingelser og forhold mellem bestanddelene og anvender cupribromid som katalysator: til en blanding af 4,8 g na-triumhydrid i 40 ml N,N-dimethylformamid sættes 20 ml 5 (27,4 g) 2,2,2-trifluorethanol. Til denne blanding sættes 0,034 mol (8,0 g) 1,4-dibrombenzen og 1,0 g cupribromid. Reaktionsblandingen opvarmes ved ca. 100 °C i to timer, hvorpå der afskrækkes med isvand. Syrning med saltsyre og filtrering giver 9,2 g (99%) hvidt fast stof 1,4-10 bis(2,2,2-trifluorethoxy)benzen. Strukturen bekræftes ved iR-spektralanalyse.The reaction is then repeated as follows, varying the conditions and ratios of the components and using cupribromide as catalyst: to a mixture of 4.8 g of sodium hydride in 40 ml of N, N-dimethylformamide is added 20 ml of 5 (27.4 g) 2 , 2,2-trifluoroethanol. To this mixture is added 0.034 moles (8.0 g) of 1,4-dibromobenzene and 1.0 g of cupribromide. The reaction mixture is heated at ca. 100 ° C for two hours, then quenched with ice water. Acidification with hydrochloric acid and filtration give 9.2 g (99%) of white solid 1,4-10 bis (2,2,2-trifluoroethoxy) benzene. The structure is confirmed by iR spectral analysis.
Følgende eksempel belyser den nyttige virkning af fremgangsmåden ifølge opfindelsen i sammenligning med en 15 kendt proces, idet fremgangsmåden ifølge opfindelsen kan give et bedre udbytte.The following example illustrates the useful effect of the method according to the invention in comparison with a known process, the method according to the invention being able to give a better yield.
EKSEMPEL 2 20 Til en blanding af 2,42 mol (334,4 g) kaliumcarbonat, 2,2 mol (510,6 g) 2,2,2-trifluorethyltrifluormethansulfonat i 1,02 liter acetone sættes en opløsning af 1,0 mol (110 g) hydroguinon i 1,1 liter acetone langsomt i løbet af 2 timer. Derpå opvarmes ved tilbagesvaling i 24 timer, reak-25 tionsblandingen inddampes, og der sættes til resten 2 liter chloroform og 2 liter vand. Chloroformlaget fraskilles, det vandige lag vaskes to gange med 1 liter chloroform, og den kombinerede chloroformopløsning vaskes med 1 liter vand. Chloroformopløsningen tørres over magnesium-30 sulfat og koncentreres derpå under vakuum. Der sættes hexan til resten, og det faste produkt samles ved filtrering og vaskes med hexan. Yderligere materiale opnås fra de koncentrerede rester. Der opnås et udbytte på 88%, 241 g 1,4-bis(2,2,2-trifluorethoxy)benzen, smp. 75-77 °C.EXAMPLE 2 To a mixture of 2.42 moles (334.4 g) of potassium carbonate, 2.2 moles (510.6 g) of 2,2,2-trifluoroethyl trifluoromethanesulfonate in 1.02 liters of acetone is added a solution of 1.0 moles (110 g) hydroguinone in 1.1 liters of acetone slowly over 2 hours. Then, reflux for 24 hours, evaporate the reaction mixture and add 2 liters of chloroform and 2 liters of water to the residue. The chloroform layer is separated, the aqueous layer is washed twice with 1 liter of chloroform, and the combined chloroform solution is washed with 1 liter of water. The chloroform solution is dried over magnesium sulfate and then concentrated under vacuum. Hexane is added to the residue and the solid product is collected by filtration and washed with hexane. Additional material is obtained from the concentrated residues. 88% yield is obtained, 241 g of 1,4-bis (2,2,2-trifluoroethoxy) benzene, m.p. 75-77 ° C.
3535
Claims (1)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2133279A | 1979-03-19 | 1979-03-19 | |
| US2133179A | 1979-03-19 | 1979-03-19 | |
| US2133179 | 1979-03-19 | ||
| US2133279 | 1979-03-19 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK112180A DK112180A (en) | 1980-09-20 |
| DK167062B1 true DK167062B1 (en) | 1993-08-23 |
Family
ID=26694559
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK112180A DK167062B1 (en) | 1979-03-19 | 1980-03-14 | METHOD FOR PREPARING 1,4-BIS (2,2,2-TRIFLUORETHOXY) BENZEN |
| DK122290A DK164857C (en) | 1979-03-19 | 1990-05-17 | METHOD FOR PREPARING 2,5-BIS (2,2,2-TRIFLUORETHOXY) -N- (2-PIPERIDYLMETHYL) BENZAMIDE |
| DK91798A DK79891D0 (en) | 1979-03-19 | 1991-04-30 | 2,5-BIS (2,2,2-TRIFLUORETHOXY) ACETOPHENONS USED AS INTERMEDIATES AND PROCEDURES FOR PRODUCING THEREOF |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK122290A DK164857C (en) | 1979-03-19 | 1990-05-17 | METHOD FOR PREPARING 2,5-BIS (2,2,2-TRIFLUORETHOXY) -N- (2-PIPERIDYLMETHYL) BENZAMIDE |
| DK91798A DK79891D0 (en) | 1979-03-19 | 1991-04-30 | 2,5-BIS (2,2,2-TRIFLUORETHOXY) ACETOPHENONS USED AS INTERMEDIATES AND PROCEDURES FOR PRODUCING THEREOF |
Country Status (14)
| Country | Link |
|---|---|
| JP (8) | JPH01104045A (en) |
| CA (1) | CA1137486A (en) |
| CH (1) | CH643829A5 (en) |
| DE (1) | DE3010195A1 (en) |
| DK (3) | DK167062B1 (en) |
| ES (1) | ES489629A0 (en) |
| FR (7) | FR2454438A1 (en) |
| GB (2) | GB2045760B (en) |
| IE (1) | IE49558B1 (en) |
| IL (1) | IL59623A (en) |
| IT (1) | IT1195262B (en) |
| NL (1) | NL191486C (en) |
| PT (1) | PT70967A (en) |
| SE (5) | SE447992B (en) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2519975A1 (en) * | 1982-01-21 | 1983-07-22 | Rhone Poulenc Spec Chim | PROCESS FOR PREPARING TRIFLUOROMETHOXY OR TRIFLUOROMETHYLTHIOPHENYLCETONES |
| FR2519979A1 (en) * | 1982-01-21 | 1983-07-22 | Rhone Poulenc Spec Chim | PROCESS FOR THE PREPARATION OF TRIFLUOROMETHOXY OR TRIFLUOROMETHYLTHIOPHENYLSULFONES |
| FR2519980A1 (en) * | 1982-01-21 | 1983-07-22 | Rhone Poulenc Spec Chim | PROCESS FOR THE SULFONYLATION OF HALOGENO OR TRIHALOGENOMETHYLBENZENES |
| FR2519974A1 (en) * | 1982-01-21 | 1983-07-22 | Rhone Poulenc Spec Chim | PROCESS FOR THE ACYLATION OF HALOGENO OR TRIHALOGENOMETHYLBENZENES |
| FR2525588A1 (en) * | 1982-04-22 | 1983-10-28 | Rhone Poulenc Spec Chim | PROCESS FOR PREPARING PHENYLCETONES FROM HALOGENO OR TRIHALOGENOMETHYLBENZENES AND ALIPHATIC OR AROMATIC TRIHALOGENOMETHYL COMPOUNDS |
| EP0175188A1 (en) * | 1984-09-11 | 1986-03-26 | Nihon Tokushu Noyaku Seizo K.K. | Carbamoylimidazole derivatives |
| US4675448A (en) * | 1985-02-13 | 1987-06-23 | Ethyl Corporation | Chlorination process |
| FR2579594B1 (en) * | 1985-03-29 | 1987-06-05 | Rhone Poulenc Spec Chim | PROCESS FOR THE PREPARATION OF TRIFLUOROETHOXY OR TRIFLUOROETHYLTHIOBENZENES |
| FR2579591B1 (en) * | 1985-03-29 | 1988-10-14 | Rhone Poulenc Spec Chim | PROCESS FOR THE PREPARATION OF PENTAFLUOROETHOXY AND PENTAFLUOROETHYLTHIOBENZENIQUE DERIVATIVES |
| NZ219913A (en) * | 1986-04-25 | 1990-08-28 | Riker Laboratories Inc | Various flecainide derivatives and antibodies raised thereto |
| EP0242847B1 (en) * | 1986-04-25 | 1993-06-02 | Abbott Laboratories | Tracers for use in flecainide fluorescence polarization immunoassay |
| DE3644798A1 (en) * | 1986-12-31 | 1988-07-14 | Hoechst Ag | NEW NITROHALOALCOXYBENZOLS, METHOD FOR THEIR PRODUCTION AND THEIR USE |
| FR2640262B1 (en) * | 1988-12-14 | 1991-05-31 | Rhone Poulenc Chimie | PROCESS FOR THE PREPARATION OF TRIFLUOROETHOXYLATED ARYLIC KETONES |
| IL120715A (en) * | 1997-04-21 | 2000-07-16 | Finetech Ltd | Process for the preparation of (2,2,2,-trifluoroethoxy)benzoic acids |
| IL121288A (en) | 1997-07-11 | 2000-10-31 | Finetech Ltd | Process and a novel intermediate for the preparation of flecainide |
| US6316627B1 (en) * | 1997-04-21 | 2001-11-13 | Fine Tech Ltd. | Process for the preparation of flecainide |
| US7196197B2 (en) | 2003-09-17 | 2007-03-27 | Apotex Pharmachem Inc. | Process for the preparation of Flecainide, its pharmaceutically acceptable salts and important intermediates thereof |
| JP4894226B2 (en) * | 2005-10-31 | 2012-03-14 | Ｄｉｃ株式会社 | Method for producing fluorine-containing liquid crystal compound having hydroquinone skeleton |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3539642A (en) * | 1967-07-19 | 1970-11-10 | Geigy Chem Corp | 2-phenyl-2-(1-naphthyl)acetamides |
| US3772304A (en) * | 1969-10-30 | 1973-11-13 | Hoffmann La Roche | 4-hydroxy-isoquinolines and processes for their preparation |
| US3719687A (en) * | 1970-07-22 | 1973-03-06 | Riker Laboratories Inc | N-(2-dialkylaminoalkylene)amides of 1,1-dihydroperfluoroalkoxy-substituted aryl acids and salts thereof |
| US3655728A (en) | 1970-07-22 | 1972-04-11 | Riker Laboratories Inc | N-(2 - dialkylaminoalkylene)-esters of fluoroalkoxy-substituted aryl carboxylic acid and salts thereof |
| US3967949A (en) * | 1973-06-18 | 1976-07-06 | Eli Lilly And Company | Fluoroalkoxyphenyl-substituted nitrogen heterocycles as plant stunting agents |
| US4169108A (en) * | 1973-08-16 | 1979-09-25 | Sterling Drug Inc. | 5(OR 6)-[(Substituted-amino)alkyl]-2,3-naphthalenediols |
| US3900481A (en) | 1974-04-01 | 1975-08-19 | Riker Laboratories Inc | Derivatives of pyrrolidine and piperidine |
| US4013670A (en) * | 1974-04-01 | 1977-03-22 | Riker Laboratories, Inc. | Derivatives of pyrrolidine and piperidine |
| US4005209A (en) * | 1974-04-01 | 1977-01-25 | Riker Laboratories, Inc. | Antiarrhythmic method utilizing fluoroalkoxy-N-piperidyl and pyridyl benzamides |
| IL49803A (en) * | 1975-06-28 | 1979-11-30 | Fisons Ltd | Preparation of pyrogallol |
| DE2616478C2 (en) * | 1976-04-14 | 1986-05-22 | Brickl, Rolf, Dr., 7951 Warthausen | Medicines, biocides and cosmetics containing fluoroacylresorcins |
| JPS6023656B2 (en) * | 1976-09-02 | 1985-06-08 | 川研フアインケミカル株式会社 | Method for producing alkoxy aromatic compounds |
| US4071524A (en) * | 1976-11-08 | 1978-01-31 | Riker Laboratories, Inc. | Derivatives of urea |
| US4097481A (en) * | 1976-11-08 | 1978-06-27 | Riker Laboratories, Inc. | Tertiary amide derivatives of pyrrolidine and piperidine |
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0
- GB GB8214964A patent/GB2097000B/en not_active Expired
-
1980
- 1980-03-04 CA CA000346919A patent/CA1137486A/en not_active Expired
- 1980-03-14 SE SE8002003A patent/SE447992B/en not_active IP Right Cessation
- 1980-03-14 IL IL59623A patent/IL59623A/en unknown
- 1980-03-14 DK DK112180A patent/DK167062B1/en not_active IP Right Cessation
- 1980-03-16 NL NL8001551A patent/NL191486C/en not_active IP Right Cessation
- 1980-03-17 ES ES489629A patent/ES489629A0/en active Granted
- 1980-03-17 DE DE19803010195 patent/DE3010195A1/en active Granted
- 1980-03-18 IE IE549/80A patent/IE49558B1/en not_active IP Right Cessation
- 1980-03-18 IT IT20746/80A patent/IT1195262B/en active Protection Beyond IP Right Term
- 1980-03-18 FR FR8006019A patent/FR2454438A1/en active Granted
- 1980-03-18 CH CH212880A patent/CH643829A5/en not_active IP Right Cessation
- 1980-03-18 PT PT70967A patent/PT70967A/en active IP Right Revival
- 1980-03-18 GB GB8009041A patent/GB2045760B/en not_active Expired
-
1981
- 1981-01-07 FR FR8100145A patent/FR2468591A1/en active Granted
- 1981-01-07 FR FR8100144A patent/FR2468590A1/en active Granted
- 1981-01-07 FR FR8100143A patent/FR2468576A1/en active Granted
- 1981-01-07 FR FR8100142A patent/FR2468571A1/en active Granted
- 1981-01-07 FR FR8100140A patent/FR2468569A1/en active Granted
- 1981-01-07 FR FR8100141A patent/FR2468570A1/en active Granted
-
1984
- 1984-03-21 SE SE8401555A patent/SE463260B/en not_active IP Right Cessation
- 1984-03-21 SE SE8401554A patent/SE447993B/en not_active IP Right Cessation
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1988
- 1988-06-01 JP JP63135363A patent/JPH01104045A/en active Granted
- 1988-06-01 JP JP63135365A patent/JPH01104044A/en active Granted
- 1988-06-01 JP JP63135367A patent/JPH01125341A/en active Granted
- 1988-06-01 JP JP63135370A patent/JPH01125344A/en active Granted
- 1988-06-01 JP JP63135366A patent/JPH01125339A/en active Granted
- 1988-06-01 JP JP63135364A patent/JPH01104043A/en active Granted
- 1988-06-01 JP JP63135369A patent/JPH01125343A/en active Granted
- 1988-06-01 JP JP63135368A patent/JPH01125342A/en active Granted
-
1989
- 1989-04-27 SE SE8901532A patent/SE463418B/en not_active IP Right Cessation
- 1989-04-27 SE SE8901533A patent/SE463419B/en not_active IP Right Cessation
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1990
- 1990-05-17 DK DK122290A patent/DK164857C/en not_active IP Right Cessation
-
1991
- 1991-04-30 DK DK91798A patent/DK79891D0/en unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B1 | Patent granted (law 1993) | ||
| PUP | Patent expired |