NO162463B - INTERMEDIATES FOR THE PREPARATION OF DERIVATIVES OF (OKSO-4-4H- (1) -BENZOPYRANE-8-YL) -ACDIC ACID. - Google Patents

INTERMEDIATES FOR THE PREPARATION OF DERIVATIVES OF (OKSO-4-4H- (1) -BENZOPYRANE-8-YL) -ACDIC ACID. Download PDF

Info

Publication number
NO162463B
NO162463B NO823939A NO823939A NO162463B NO 162463 B NO162463 B NO 162463B NO 823939 A NO823939 A NO 823939A NO 823939 A NO823939 A NO 823939A NO 162463 B NO162463 B NO 162463B
Authority
NO
Norway
Prior art keywords
singlet
phenyl
mol
methyl
methoxy
Prior art date
Application number
NO823939A
Other languages
Norwegian (no)
Other versions
NO162463C (en
NO823939L (en
Inventor
Philippe Briet
Jean-Jacques Berthelon
Francois Collonges
Original Assignee
Lipha
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lipha filed Critical Lipha
Publication of NO823939L publication Critical patent/NO823939L/en
Publication of NO162463B publication Critical patent/NO162463B/en
Publication of NO162463C publication Critical patent/NO162463C/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
    • C07D311/36—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only not hydrogenated in the hetero ring, e.g. isoflavones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrane Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Description

Oppfinnelsen vedrører mellomprodukter for fremstilling av The invention relates to intermediate products for the production of

derivater av [okso-4-4H-(l)-benzopyran-8-yl]-eddiksyre med formel I: derivatives of [oxo-4-4H-(1)-benzopyran-8-yl]-acetic acid of formula I:

hvor AR representerer et fenylradikal som er substituert eller ikke en eller to ganger med et lavere alkylradikal eller et lavere alkoksyradikal, representerer et hydrogenatom eller et fenylradikal, R2 representerer et hydrogenatom eller et alkalimetall, et oksetylert alkylradikal, hydroksyetyl-, where AR represents a phenyl radical which is substituted or unsubstituted once or twice with a lower alkyl radical or a lower alkoxy radical, represents a hydrogen atom or a phenyl radical, R 2 represents a hydrogen atom or an alkali metal, an oxytylated alkyl radical, hydroxyethyl-,

dietylaminoety1-, dimetylaminopropy1-, morfolinoety1-radikal, diethylaminoethyl1-, dimethylaminopropyl1-, morpholinoethyl1-radical,

og X representerer et hydrogenatom eller et lavere alkoksyradikal. and X represents a hydrogen atom or a lower alkoxy radical.

Fremstilling av disse eddiksyrederivatene er beskrevet i Preparation of these acetic acid derivatives is described in

norsk patent nr. 159169, og de er anvendelige i terapeutiske preparater - særlig i antitumormedikamenter. Norwegian patent no. 159169, and they are applicable in therapeutic preparations - especially in antitumor drugs.

Mellomproduktene i henhold til oppfinnelsen er karakterisert ved at de er 8-bromalkyl-4H-(l)-benzopyran-4-oner med den generelle formel II: The intermediates according to the invention are characterized in that they are 8-bromoalkyl-4H-(1)-benzopyran-4-ones with the general formula II:

hvor AR, Ri og X er som definert ovenfor. where AR, Ri and X are as defined above.

Halogenbenzopyranonene som tilsvarer formel II kan The halobenzopyranones corresponding to formula II can

fremstilles ved en av de tre følgende fremgangsmåter med gode utbytter. is produced by one of the three following methods with good yields.

Nedenstående reaksjonsskjerna er gitt for brom-metyl-8-fenyl-2-4H- [1]-benzopyran-4-on. The reaction core below is given for bromo-methyl-8-phenyl-2-4H-[1]-benzopyran-4-one.

Metode A Method A

I henhold til den preparative sekvens i metode A behandler man i et første trinn en utgangsforbindelse med formélen: hvor X og er som definert for formel (II) og R2er hydrogen eller lavere alkyl, med polyoksymetylen i nærvær av konsentrert saltsyre for oppnåelse av et klormetylfenylketon med formel: According to the preparative sequence in method A, a starting compound is treated in a first step with the formelene: where X and is as defined for formula (II) and R2 is hydrogen or lower alkyl, with polyoxymethylene in the presence of concentrated hydrochloric acid to obtain a chloromethylphenyl ketone with formula:

hvor , R_ og x har samme betydninger som angitt ovenfor. where , R_ and x have the same meanings as given above.

I annet trinn kondenseres det klormetylerte mellomprodukt (IV) med metanol og omdannes således til metoksymetylert mellomprodukt med formel: In the second step, the chloromethylated intermediate (IV) is condensed with methanol and thus converted into a methoxymethylated intermediate with the formula:

I et tredje trinn kondenseres det oppnådde mellomprodukt med en ester med formel AR-COOEt hvor AR er fenyl, substituert fenyl - med lavere alkyl, lavere alkoksy eller halogen - tenyl, pyridyl, furyl, naftyl, alkyl, cykloalkyl, aralkyl, og omdannes til propandioner-1,3 med følgende formel: In a third step, the obtained intermediate is condensed with an ester of the formula AR-COOEt where AR is phenyl, substituted phenyl - with lower alkyl, lower alkoxy or halogen - thenyl, pyridyl, furyl, naphthyl, alkyl, cycloalkyl, aralkyl, and is converted to Propane ions-1,3 with the following formula:

hvor AR, R^ , R. og X har de samme betydninger som angitt tidligere . where AR, R^, R. and X have the same meanings as stated previously.

I det siste trinn oppnås bromalkyl-8-4H-[l]-benzopyran-4-onene, ved cyklisering av propandion-1,3-ene med formel VI i nærvær av bromhydrogensyre• In the last step, the bromoalkyl-8-4H-[l]-benzopyran-4-ones are obtained by cyclization of the propanedione-1,3s of formula VI in the presence of hydrobromic acid•

Metode B Method B

I et første trinn behandles metyl-metoksy-2-metyl-3-benzpat med formel hvor X har samme betydning som angitt tidligere, med bromsuksinimid. Det oppnådde metyl-brometyl-3-metoksy-2-benzoat med formel kondenseres med natriunme^ylat, i metanolisk miljø, for omdannel-se til metyl-metoksymetyl-3-metoksy-2-benzoat med formel In a first step, methyl-methoxy-2-methyl-3-benzpate of formula where X has the same meaning as stated earlier is treated with bromosuccinimide. The obtained methyl-bromomethyl-3-methoxy-2-benzoate of formula is condensed with sodium meylate, in a methanolic environment, to convert into methyl-methoxymethyl-3-methoxy-2-benzoate of formula

I en tredje preparativ sekvens og spesielt i det tilfel-le hvor AR = R = fenyl eller AR = H og R = fenyl, er det vist at det er mulig å komme frem til den forbindelse som tilsvarer formel (I) i henhold til følgende skjema: In a third preparative sequence and especially in the case where AR = R = phenyl or AR = H and R = phenyl, it has been shown that it is possible to arrive at the compound corresponding to formula (I) according to the following form:

I det følgende skal det gis eksempler som illustrerer oppfinnelsen. In the following, examples will be given that illustrate the invention.

Eksempel 1: Example 1:

( Klormetyl- 3- hydroksy- 2- fenyl)- 1- etanon CgHgCl02( Chloromethyl- 3- hydroxy- 2- phenyl)- 1- ethanone CgHgCl02

PM = 184 ,62 . PM = 184 .62 .

Man oppvarmer en blanding av 2,723 kg (20 mol) (hydroksy-2-fenyl)-1-etanon, 600,6 g (20 mol) polyoksymetylen og 15 liter konsentrert saltsyre til 50-60°C i 7 timer. Man ekstraherer med benzen, vasker til nøytralitet med en vandig løsning av natriumbikarbonat og fordamper løsningsmidlet under vakuum. Man opplø-ser fordampningsresten i 2,25 liter karbontetraklorid og 1.5 liter heksan i varme, lar det henstå en natt ved 5°C og filtrerer utfellingsproduktet av klormetyl-5-hydroksy-2-fenyl) - 1-etanon. Filtratet inndampes under vakuum og destilleres idet man er omhyggelig med at temperaturen i kokeren ikke passerer 200°C. Man oppsamler en fraksjon som destillerer mellom 130 og 146°C under 0,8 mm Hg som krystalliserer ved omgivelsestemperatur, og som er en blanding av (klormetyl-5 og klormetyl-3-hydroksy-2-fenyl)-1-etanon. Denne fraksjon oppvarmes til smelt-ing (mot 80°C) og tømmes langsomt ned i heksan under energisk om-røring (500 ml for 100 g). Man lar røringen fortsette i 30 minutter og filtrerer så utfellingsproduktet av (klormetyl-5-hydroksy-2-fenyl)-1-etanon. Man lar filtratet hvile én natt, separerer en uløselig olje ved dekantering- og konsentrerer så blandingen lett. Man filtrerer'utfellingsproduktet som er oppnådd, og tørker det ved vanlig temperatur. PFq: 4 5°C, IR: v c: = 0 = 1640 cm"<1>, RMN (CCl^ 6 i ppm i forhold til TMS, 3 H ved 2.6 (singlett) , 2 H ved 4,62 (singlett) , 1 H ved 6,94 (triplett) , 2 H fra 7,5 til 7,8 (multiplett), 1 H 12,6 (singlett) utbyttbar med D2O. A mixture of 2.723 kg (20 mol) (hydroxy-2-phenyl)-1-ethanone, 600.6 g (20 mol) polyoxymethylene and 15 liters of concentrated hydrochloric acid is heated to 50-60°C for 7 hours. Extract with benzene, wash to neutrality with an aqueous solution of sodium bicarbonate and evaporate the solvent under vacuum. The evaporation residue is dissolved in 2.25 liters of carbon tetrachloride and 1.5 liters of hexane in heat, left overnight at 5°C and the precipitated product of chloromethyl-5-hydroxy-2-phenyl)-1-ethanone is filtered. The filtrate is evaporated under vacuum and distilled, being careful that the temperature in the reboiler does not exceed 200°C. A fraction is collected which distills between 130 and 146°C below 0.8 mm Hg, which crystallizes at ambient temperature, and which is a mixture of (5-chloromethyl and chloromethyl-3-hydroxy-2-phenyl)-1-ethanone. This fraction is heated to melting (towards 80°C) and slowly emptied into hexane with vigorous stirring (500 ml for 100 g). Stirring is allowed to continue for 30 minutes and the precipitated product of (chloromethyl-5-hydroxy-2-phenyl)-1-ethanone is then filtered. The filtrate is allowed to rest overnight, an insoluble oil is separated by decantation and the mixture is then lightly concentrated. The precipitate product obtained is filtered and dried at ordinary temperature. PFq: 4 5°C, IR: v c: = 0 = 1640 cm"<1>, RMN (CCl^ 6 in ppm relative to TMS, 3 H at 2.6 (singlet) , 2 H at 4.62 (singlet) , 1 H at 6.94 (triplet) , 2 H from 7.5 to 7.8 (multiplet), 1 H 12.6 (singlet) exchangeable with D2O.

Eksempel 2 Example 2

(H ydroksy- 2- metoksymetyl- 3- fenyl)- 1- etanon cl0<H>12°3 PM = 180,2 (H ydroxy- 2- methoxymethyl- 3- phenyl)- 1- ethanone cl0<H>12°3 PM = 180.2

Man oppvarmer ved tilbakeløpskjøling en blanding av 184,6 g (1 mol) av (klormetyl-3-hydroksy-2-fenyl)-1-etanon, 1,5 liter metanol og 103 ml konsentrert saltsyre. Man tilsetter straks, i små fraksjoner 167,5 g (3 mol) av jernpulver i 1 time og 20 minutter. Deretter foretar man tilbakeløpskjøling i 2 timer og 30 minutter, og lar blandingen avkjøle én natt og filtrerer. Man konsentrerer filtratet under vakuum til ca. 500 ml, nøytraliserer med en vandig løsning av natriumbikarbonat, ekstraherer med kloroform, vasker med vann, fordamper løsningsmidlet under vakuum og destillerer. Eb^ : <8>9-91°C, Rdt: 88 %, I.R.:v c = 0; 1640 A mixture of 184.6 g (1 mol) of (chloromethyl-3-hydroxy-2-phenyl)-1-ethanone, 1.5 liters of methanol and 103 ml of concentrated hydrochloric acid is heated under reflux. 167.5 g (3 mol) of iron powder are added immediately, in small fractions, for 1 hour and 20 minutes. Reflux is then carried out for 2 hours and 30 minutes, and the mixture is allowed to cool overnight and filtered. The filtrate is concentrated under vacuum to approx. 500 ml, neutralize with an aqueous solution of sodium bicarbonate, extract with chloroform, wash with water, evaporate the solvent under vacuum and distil. Eb^ : <8>9-91°C, Rdt: 88%, I.R.: v c = 0; 1640

_, 0,3 mm _, 0.3 mm

cm . RMH <CC14) 6 i ppm i forhold til TMS 3 H ved 2,58 (singlett) , 3 H ved.3,40 (singlett), 2 H ved 4,46 (singlett), 1 H ved 6,90 (triplett), 2 H fra 7,3 til 7,7 (multiplett), 1 H ved 12,6 cm. RMH <CC14) 6 in ppm relative to TMS 3 H at 2.58 (singlet), 3 H at 3.40 (singlet), 2 H at 4.46 (singlet), 1 H at 6.90 (triplet ), 2 H from 7.3 to 7.7 (multiplet), 1 H at 12.6

(singlett ) utbyttbar med ^ 2^' (singlet ) interchangeable with ^ 2^'

Eksempel 3 Example 3

( Hydroksy- 2- metoksymet. yl- 3- f enyl) - 1- f enyl- 3- propandion- l, 3 C17H16°4' PM = 284 '31' (Hydroxy- 2- methoxymeth. yl- 3- phenyl) - 1- phenyl- 3- propanedione- 1, 3 C17H16°4' PM = 284 '31'

Man oppvarmer under tilbakeløpskjøling en blanding av 207 g (1,38 mol) etylbenzoat, 740 ml vannfritt benzen og 124 g (2,58 mol) av en 50 % natriumhydridsuspensjon i olje. Man tilsetter så dråpevis, i løpet av 2 timer, en løsning av • 167 g (0,93 mol) A mixture of 207 g (1.38 mol) of ethyl benzoate, 740 ml of anhydrous benzene and 124 g (2.58 mol) of a 50% sodium hydride suspension in oil is heated under reflux. A solution of • 167 g (0.93 mol) is then added dropwise over the course of 2 hours

(hydroksy-2-metoksymetyl-3-fenyl)-1-etanon i 415 ml vannfritt (hydroxy-2-methoxymethyl-3-phenyl)-1-ethanone in 415 ml anhydrous

benzen. Man oppvarmer så i 2 timer under tilbakeløp, avkjøler og tilsetter dråpevis 300 ml etanol. Man fordamper ca. 700 ml løs-ningsmiddel/avkjøler og tar resten opp med 1,5 1 benzen og 1,8 1 av 3 N saltsyre. Man rører i 1 time, dekanterer, ekstraherer vannfasen med benzen, vasker med vann og inndamper under vakuum. Man rekrystalliserer det oppnådde produkt i 2 liter heksan. Man oppnår 215 g (Rdt: 81 %) av et faststoff som smelter mot 55°C, IR; v C = 0 = 1610 era"<1.>benzene. It is then heated for 2 hours under reflux, cooled and 300 ml of ethanol is added dropwise. One evaporates approx. 700 ml of solvent/coolant and take up the remainder with 1.5 1 of benzene and 1.8 1 of 3 N hydrochloric acid. Stir for 1 hour, decant, extract the aqueous phase with benzene, wash with water and evaporate under vacuum. The product obtained is recrystallized in 2 liters of hexane. 215 g (Rdt: 81%) of a solid melting at 55°C, IR are obtained; v C = 0 = 1610 era"<1.>

Eksempel 4 Example 4

Brom- metyl- 8- fenyl- 2- 4H-[ 1]- benzopyran- 4- on C1gH1^Br02Bromo- methyl- 8- phenyl- 2- 4H-[ 1]- benzopyran- 4- one C1gH1^Br02

PM = 315,17. PM = 315.17.

Man oppvarmer en blanding av 361 g (1,40 mol) av (hydroksy-2-metoksy-metyl-3-fenyl)-1-fenyl-3-propandion-l,3, 1,4 1 eddiksyre og 917 ml av 62 % bromhydrogensyre i 3 timer ved 70°C. Man tømmer så dette ned i 5 ml kaldt vann, filtrerer, vasker med vann og rekrystalliserer i aceton. Man oppnår 207,4 g (Rdt: A mixture of 361 g (1.40 mol) of (hydroxy-2-methoxy-methyl-3-phenyl)-1-phenyl-3-propanedione-1,3,1,4 1 acetic acid and 917 ml of 62 % hydrobromic acid for 3 hours at 70°C. This is then emptied into 5 ml of cold water, filtered, washed with water and recrystallized in acetone. 207.4 g is obtained (Rdt:

47 %) av et hvitt faststoff. PF„: 182-183°C. IR: v c = 0 : 47%) of a white solid. MP: 182-183°C. IR: v c = 0 :

-1 1650 cm . RMN (DMS0) 6 i ppm i forhold til TMS, 2 H ved 5,02 (singlett), 1 H ved 7,02 (singlett), 8 H fra 7,3 til 8,3 (multiplett). -1 1650 cm. RMN (DMS0) 6 in ppm relative to TMS, 2 H at 5.02 (singlet), 1 H at 7.02 (singlet), 8 H from 7.3 to 8.3 (multiplet).

E ksempel 5 Example 5

Metyl- metoksy- 2- metyl- 3- benzoat Cl0H12°3- PM = 180,20. Methyl- methoxy- 2- methyl- 3- benzoate Cl0H12°3- PM = 180.20.

I en reaktor imf ører man en løsning av 852 g (21,3 mol) natriumhydroksyd i 10 1 vann. Man tilsetter så en løsning av 1,05 kg (7 mol) 3-metylsalicylsyre i 10 1 metylenklorid og deretter 212,7 g (0,68 mol) benzyltributylammoniumklorid. Deretter kommer 2 ,662 1 (27 ,9 moi) dimetylsul fat. Temperaturen stiger lett. Man agiterer så reaksjonsmiljøet i 24 timer ved'omgivelsestemperatur. Den organiske fase dekanteres og behandles så under agitering i 2 timer med 10 1 av en 15 % ammoniakkløsning. Man dekanterer, fordamper metylénkloridet under- vakuum, tar opp den oppnådde olje med 7 1 heksan under agitering, og etter tørk-ing over Na2S04 og fordampning av løsningsmidlet oppnår man en væske som man destillerer: PE0 12 70-73°C, IR: v c = .0 = 1720 cm"<1>, oppnådd vekt: 1,131'kg (Rdt 89,7 %). RMN (CDC13) 6 i ppm i forhold til TMS, 3 H ved 2,25 (singlett), 3 H ved 3,8 (singlett), 3 H ved 3,85 (singlett), 3 H fra 6,85 til 7,7 (multiplett) ... A solution of 852 g (21.3 mol) sodium hydroxide in 10 1 water is introduced into a reactor. A solution of 1.05 kg (7 mol) of 3-methylsalicylic acid in 10 1 of methylene chloride is then added and then 212.7 g (0.68 mol) of benzyltributylammonium chloride. Next comes 2.662 1 (27.9 moi) of dimethylsulphate. The temperature rises easily. The reaction medium is then agitated for 24 hours at ambient temperature. The organic phase is decanted and then treated with agitation for 2 hours with 10 1 of a 15% ammonia solution. One decants, evaporates the methylene chloride under vacuum, takes up the oil obtained with 7 1 of hexane while stirring, and after drying over Na2S04 and evaporation of the solvent, one obtains a liquid which is distilled: PE0 12 70-73°C, IR: v c = .0 = 1720 cm"<1>, weight obtained: 1.131'kg (Rdt 89.7%). RMN (CDC13) 6 in ppm relative to TMS, 3 H at 2.25 (singlet), 3 H at 3.8 (singlet), 3 H at 3.85 (singlet), 3 H from 6.85 to 7.7 (multiplet) ...

Eksempel 6 Example 6

Metyl- brom- metyl- 3- metoksy- 2- benzoat C1(3H11 Br03~ PM = 2 59 ,1 . Methyl- bromo- methyl- 3- methoxy- 2- benzoate C1(3H11 Br03~ PM = 2 59 .1 .

I en reaktor anbringes 1,030 kg (5,71 mol) metyl-metoksy-2-metyl-3-benzoat, 1,118 kg (6,28 mol) N-bromsuksinimid og 28,3g azobis-isobutyronitril i"10 1 karbontetraklorid. Dette bringes 1 7 timer til tilbakeløpskjøling. Man avkjøler til 20°C og filtrerer det dannede suksinimid. Løsningsmidlet fordampes under vakuum, og den oppnådde oransjefarvede olje dispergeres under rø-ring i 3 liter heksan. Etter 1 time avvannes det hvite utfellingsprodukt som har dannet seg og tørkes. Oppnådd vekt: 1,075 kg (Rdt: 72,7 %). PFQ: 49-53°C. IR: v c =0 : 1720 cm"<1>. RMN (CC14) 6 ppm i forhold til TMS, 3 H ved 3,85 (singlett), 3 H ved 3,90 (singlett), 2 H ved 4,55 (singlett), 3 H fra 6,85 til 7,85 (multiplett). In a reactor, 1.030 kg (5.71 mol) methyl-methoxy-2-methyl-3-benzoate, 1.118 kg (6.28 mol) N-bromosuccinimide and 28.3 g azobis-isobutyronitrile are placed in "10 1 carbon tetrachloride. This is brought 17 hours to reflux. Cool to 20°C and filter the formed succinimide. The solvent is evaporated under vacuum, and the orange-colored oil obtained is dispersed with stirring in 3 liters of hexane. After 1 hour, the white precipitate that has formed is dewatered and dried. Weight obtained: 1.075 kg (Rdt: 72.7%). PFQ: 49-53°C. IR: v c =0 : 1720 cm"<1>. RMN (CC14) 6 ppm relative to TMS, 3 H at 3.85 (singlet), 3 H at 3.90 (singlet), 2 H at 4.55 (singlet), 3 H from 6.85 to 7, 85 (multiplet).

Eksempel 7 Example 7

Metyl- metoksymetyl- 3- metoksy- 2- be. nzoat <c>n<H>i4°4 " PM: 210,2 3 Methyl- methoxymethyl- 3- methoxy- 2- be. nzoate <c>n<H>i4°4 " PM: 210.2 3

I en reaktor anbringer man 1,205 kg (4,65 mol) metyl-brom-metyl-3-metoksy-2-benzoat og 5,39 liter vannfri metanol. Man tilsetter straks, langsomt, 1,5 liter av en 20 % løsning av natriummetylat i metanol (f.eks. 5,38 mol natriummetylat). Reak-sjonsblandinyen bringes'deretter i 4 timer til tilbakeløp. Etter fordampning av løsningsmidlene oppnår man et pastaformig residu-um som tas opp i vann og ekstraheres med etylacetat. Man tørker, inndamper og destillerer inndampningsresten under vakuum. PE0 06mm: 87_95°c- Oppnådd vekt: 777,5 g (Rdt: 79,5 %). IR: v c = 0 : 1725 cm"<1.> RMN ,(CC14) 6 i ppm i forhold til TMS, 3 H ved 3,4 (singlett), 3 H ved 3,8 (singlett), 3 H ved 3,9 (singlett), 2 H ved 4,5 (singlett), 3 H fra 6,95 til 7,8 (multiplett). 1.205 kg (4.65 mol) of methyl-bromo-methyl-3-methoxy-2-benzoate and 5.39 liters of anhydrous methanol are placed in a reactor. One immediately adds, slowly, 1.5 liters of a 20% solution of sodium methylate in methanol (e.g. 5.38 mol sodium methylate). The reaction mixture is then refluxed for 4 hours. After evaporation of the solvents, a pasty residue is obtained which is taken up in water and extracted with ethyl acetate. The evaporation residue is dried, evaporated and distilled under vacuum. PE0 06mm: 87_95°c- Achieved weight: 777.5 g (Rdt: 79.5 %). IR: v c = 0 : 1725 cm"<1.> RMN ,(CC14) 6 in ppm relative to TMS, 3 H at 3.4 (singlet), 3 H at 3.8 (singlet), 3 H at 3 .9 (singlet), 2 H at 4.5 (singlet), 3 H from 6.95 to 7.8 (multiplet).

Eksempel 8 Example 8

Brom- metyl- 8- f enyl- 2- 4H- [ 1] - benzopyran- 4- on C <gH>^<B>r02Bromo- methyl- 8- phenyl- 2- 4H- [ 1] - benzopyran- 4- one C<gH>^<B>r02

PM = 3J5,17. PM = 3J5.17.

I en reaktor anbringer man 880 ml vannfri dioksari og 880 ml of anhydrous dioxarium are placed in a reactor and

84,5 g (1,76 mol) natriumhydrid. Man bringer blandingen til 80°C og tilsetter dråpevis under agitering en blanding av 277 g 84.5 g (1.76 mol) of sodium hydride. The mixture is brought to 80°C and a mixture of 277 g is added dropwise while stirring

(1,32 mol) metyl-metoksymetyl-3-metoksy-2-benzoat og 105,7 g (0,88 mol) acetofenon. Man fortsetter så oppvarmningen ved 80°C i 3 timer. Etter avkjøling tilsetter man under røring 7 liter heksan. Man lar henstå natten over. Utfellingsproduktet som har dannet seg, avvannes og innføres i små porsjoner i en blanding av 1,3 1 eddiksyre, 2,6 1 vann og 2,6 1 benzen. Den organiske fase dekanteres, 'vaskes med en løsning av natriumbikarbonat, tørkes og løsningsmidlet fordampes under vakuum. Man oppnår 227,4 g av en olje som man anvender uten rensning i følgen-de trinn. Denne olje solubiliseres i 911 ml eddiksyre. Man tilsetter 650 ml av 62 % bromhydrogensyre, og blandingen bringes i 3 timer til 80°C. Man avkjøler til 40°C og tømmer blandingen under røring ned i 12 liter vann. Utfellingsproduktet som dan-ner seg, filtreres, vaskes med vann og rekrystalliseres i aceton. Oppnådd vekt: 123 a (Rdt: 51,3 %), PF„: 182-183°C. (1.32 mol) methyl-methoxymethyl-3-methoxy-2-benzoate and 105.7 g (0.88 mol) acetophenone. The heating is then continued at 80°C for 3 hours. After cooling, 7 liters of hexane are added while stirring. Leave to stand overnight. The precipitation product that has formed is dewatered and introduced in small portions into a mixture of 1.3 1 acetic acid, 2.6 1 water and 2.6 1 benzene. The organic phase is decanted, washed with a solution of sodium bicarbonate, dried and the solvent evaporated under vacuum. 227.4 g of an oil is obtained which is used without purification in the following steps. This oil is solubilized in 911 ml of acetic acid. 650 ml of 62% hydrobromic acid is added, and the mixture is brought to 80°C for 3 hours. Cool to 40°C and pour the mixture into 12 liters of water while stirring. The precipitation product that forms is filtered, washed with water and recrystallized in acetone. Weight obtained: 123 a (Rdt: 51.3%), PF„: 182-183°C.

Eksempel 9 Example 9

Brom- metyl- 8- ( metyl- 4- f enyl) - 2- 4H- [ 1] - benzopyran^- 4- on C]7H13Br02. PM = 329,20. Bromo- methyl- 8- ( methyl- 4- phenyl)- 2- 4H- [ 1] - benzopyran^- 4- one C] 7 H 13 BrO 2 . PM = 329.20.

Fremstilt i henhold til eksempel 8 ut fra 51,1 g (0,38 mol) av (metyl-4-fenyl)-1-etanon, 120 g (0,571 mol) av metyl-metoksy-2-metoksymetyl-3-benzoat. Etter isoleiing tas den oppnådde olje opp i 348 ml eddiksyre og 348 ml.av 62 % bromhydrogensyre. Oppnådd vekt: 52,3 g (Rdt: 41,8 %), PF„: 191°C (tolu--1 Prepared according to Example 8 from 51.1 g (0.38 mol) of (methyl-4-phenyl)-1-ethanone, 120 g (0.571 mol) of methyl-methoxy-2-methoxymethyl-3-benzoate. After isolation, the obtained oil is taken up in 348 ml of acetic acid and 348 ml of 62% hydrobromic acid. Weight obtained: 52.3 g (Rdt: 41.8 %), PF„: 191°C (toluene--1

en), IR: v c = 0 (pyron): 1640 cm . RMN (DMSO) 6 i ppm i forhold til TMS, 3 H ved 2,4 (singlett), 2 H ved 5,1 (singlett), a), IR: v c = 0 (pyron): 1640 cm . NMR (DMSO) 6 in ppm relative to TMS, 3 H at 2.4 (singlet), 2 H at 5.1 (singlet),

1 H ved 7 (singlett), 7 H fra 7,3 til 8,3 (multiplett). 1 H at 7 (singlet), 7 H from 7.3 to 8.3 (multiplet).

Eksempel 10 Example 10

Brbm- metyl- 8-( metoksy- 4- feny1)- 2- 4H-[ 1]- benzopyran- 4- on <C>17<H>13Br03. PM = 345,20 Brbm-methyl-8-(methoxy-4-phenyl)-2-4H-[1]-benzopyran-4-one <C>17<H>13BrO3. PM = 345.20

Fremstilt i henhold til eksempel 8 ut fra 57,14 g (0,38 mol) av (metoksy-4-fenyl)-1-etanon, 120 g (0,571 mol) av metyl-metoksy-2-metoksymetyl-3-benzoat. Etter isolering tas den oppnådde olje opp i 4 57 mi eddiksyre og 325 ml av 62 % bromhydro-qensyre. Oppnådd vekt:: 78 g (Rdt: 59,4 °a) , PF : 165°C (toluen) . Prepared according to Example 8 from 57.14 g (0.38 mol) of (methoxy-4-phenyl)-1-ethanone, 120 g (0.571 mol) of methyl-methoxy-2-methoxymethyl-3-benzoate. After isolation, the obtained oil is taken up in 457 ml of acetic acid and 325 ml of 62% hydrobromic acid. Weight obtained:: 78 g (Rdt: 59.4 °a) , PF: 165°C (toluene).

-1 -1

IR: v c = 0 (pyron): 1640 cm . RMN (CDCl^) 6 i ppm i forhold til TMS, 3 H ved 3,8 (singlett), 2 H ved 4,8 (singlett), 1 H ved 6,75 (singlett), 7 H fra 7 til 8,3 (multiplett). IR: v c = 0 (pyrone): 1640 cm . NMR (CDCl^) 6 in ppm relative to TMS, 3 H at 3.8 (singlet), 2 H at 4.8 (singlet), 1 H at 6.75 (singlet), 7 H from 7 to 8, 3 (multiplet).

Eksempel 11 Example 11

Brom- metyl- 8-( klor- 4- fenyl)- 2- 4H-[ 1]- benzopyran- 4- on C16H10BrC102' PM = 349'62'Bromo-methyl-8-(chloro-4-phenyl)-2-4H-[1]-benzopyran-4-one C16H10BrC102' PM = 349'62'

Fremstilt i henhold til eksempel 8 ut fra 58,8 g (0,38 mol) : av (klor-4-fenyl)-1-etanon, 120 g (0,571 mol) av metyl-metoksy-2-metoksymetyl-3-benzoat. Etter isolering tas den oppnådde olje opp i 340 ml eddiksyre og 24 5 ml av 6 2 % bromhydrogensyre. Oppnådd vekt: 45,8 g (Rdt-: 34,4 %) . PF„: 228-230°C (-toluen). IR: -1 Prepared according to Example 8 from 58.8 g (0.38 mol) : of (chloro-4-phenyl)-1-ethanone, 120 g (0.571 mol) of methyl-methoxy-2-methoxymethyl-3-benzoate . After isolation, the obtained oil is taken up in 340 ml of acetic acid and 24 5 ml of 6 2% hydrobromic acid. Achieved weight: 45.8 g (Rdt-: 34.4%) . PF„: 228-230°C (-toluene). IR: -1

v c = 0 (pyron): 1640 cm . RMN (CDC13>'6 i ppm i forhold til TMS, 2 H ved 4,8 (singlett), 1 H ved 6,8 (singlett), 7 H fra v c = 0 (pyron): 1640 cm . NMR (CDC13 >'6 in ppm relative to TMS, 2 H at 4.8 (singlet), 1 H at 6.8 (singlet), 7 H from

7.2 til 8,2 (multiplett). 7.2 to 8.2 (multiplet).

Eksempel 12 Example 12

Brom- metyl- 8-( pyridyl- 3)- 2- 4H- [ 1]- benzopyran- 4- on Bromo- methyl- 8-( pyridyl- 3)- 2- 4H- [ 1]- benzopyran- 4- one

C15Hl0BrN02. PM = 316,16. C15Hl0BrN02. PM = 316.16.

Fremstilt i henhold til eksempel 8- ut fra 46,1 g (0,38 mol) av (pyridyl-3)-1-etanon og 120 g (0,571 mol) metyl-metoksy-2-metoksymetyl-3-benzoat. Etter isolering behandles oljen med 400 ml eddiksyre og 275 ml av 62 % bromhydrogensyre. Produktet isoleres i form av bromhydratet. Prepared according to example 8- from 46.1 g (0.38 mol) of (pyridyl-3)-1-ethanone and 120 g (0.571 mol) methyl-methoxy-2-methoxymethyl-3-benzoate. After isolation, the oil is treated with 400 ml of acetic acid and 275 ml of 62% hydrobromic acid. The product is isolated in the form of the bromine hydrate.

<C>15<H>llBr2N02' PM '= 397 '08- Oppnådd vekt: 76,6 g (Rdt: 50,8 %). IR: v c = 0 (pyron): 1640 cm"<1>, v NH <f> : 2400-2800 cm"<1.> Rf-IN (DMSO) 6 i ppm i forhold til TMS. 2 H ved 5,2 (singlett), 1 H ved 6,8 (massivt utbyttbar med D20), 5 H fra 7 til 8.3 (multiplett), 3 H fra 8,8 til 9,8 (multiplett). <C>15<H>llBr2N02' PM '= 397 '08- Weight obtained: 76.6 g (Rdt: 50.8%). IR: v c = 0 (pyrone): 1640 cm"<1>, v NH <f> : 2400-2800 cm"<1.> Rf-IN (DMSO) 6 in ppm relative to TMS. 2 H at 5.2 (singlet), 1 H at 6.8 (massively exchangeable with D20), 5 H from 7 to 8.3 (multiplet), 3 H from 8.8 to 9.8 (multiplet).

Eksempel 13 Example 13

,(^ lor- 5- hydroksy- 2- metoksymetyl- 3- f enyl) - 1- etanon <C>10<H>llCl03* PM = 214'65-,(^ lor- 5- hydroxy- 2- methoxymethyl- 3- phenyl) - 1- ethanone <C>10<H>llCl03* PM = 214'65-

I en reaktor anbringer man en løsning av natrium-metylat fremstilt av 28,6 g (1,245 mol) natrium og 930 ml metanol. Man tilsetter så en løsning av (klor-5-klormetyl-3-hydroksy-2-fenyl)-1-etanon i 230 ml metanol. Blandingen bringes i 2 timer til tilbakeløp. Løsningsmidlet fordampes så, og inndampningsresten tas opp med fortynnet eddiksyre. Man ekstraherer med etylacetat, og etter tørking og inndampning destilleres den oppnådde olje under nedsatt trykk. Oppnådd vekt: 69,4 g (Rdt: .28 %). PE» , = 121-131°C, IR: v c = 0 (keton): 1650 era"1. 0,6 mm RMN (CDC13) 6 i ppm i forhold til TMS, 3 H ved 2,6 (singlett), 3 H ved 3,4 (singlett), 2 H ved 4,5 (singlett), 2 H fra 7,4 til 7,7 (massivt), 1 H ved 12,5 (utbyttbar med D20). A solution of sodium methylate prepared from 28.6 g (1.245 mol) of sodium and 930 ml of methanol is placed in a reactor. A solution of (chloro-5-chloromethyl-3-hydroxy-2-phenyl)-1-ethanone in 230 ml of methanol is then added. The mixture is refluxed for 2 hours. The solvent is then evaporated, and the evaporation residue is taken up with dilute acetic acid. It is extracted with ethyl acetate, and after drying and evaporation, the oil obtained is distilled under reduced pressure. Achieved weight: 69.4 g (Rdt: .28%). PE» , = 121-131°C, IR: v c = 0 (ketone): 1650 era"1. 0.6 mm RMN (CDC13) 6 in ppm relative to TMS, 3 H at 2.6 (singlet), 3 H at 3.4 (singlet), 2 H at 4.5 (singlet), 2 H from 7.4 to 7.7 (massive), 1 H at 12.5 (exchangeable with D20).

eksempel 14 example 14

Brom- metyl- 8- klor- 6- fenyl- 2- 4H-[ 1]- benzopyran- 4- on C16H10BrC102" PM = 349'62- Bromo- methyl- 8- chloro- 6- phenyl- 2- 4H-[ 1]- benzopyran- 4- one C16H10BrC102" PM = 349'62-

Fremstilt i henhold til eksempel 3 ut fra 69 g (0,32 mol) av (klor-5-hydroksy-2-metoksy-metyl-3-fenyl)-1-etanon og 72,3 g (0,48 mol) av etylbenzoat. Det intermediære (klor-5-hydroksy-2-metoksymety1-3-fenyl)-1-fenyl-3-propandion isoleres 100°C). Ved behandling med 300 ml eddiksyre og 210 ml bromhydrogensyre oppnår man det ventede produkt. Oppnådd vekt: 61,2 g (Rdt: 54,7 %), PF,, = 210°C (toluen), IR: v c = 0 (pyron): -1 Prepared according to Example 3 from 69 g (0.32 mol) of (chloro-5-hydroxy-2-methoxy-methyl-3-phenyl)-1-ethanone and 72.3 g (0.48 mol) of ethyl benzoate. The intermediate (chloro-5-hydroxy-2-methoxymethyl-3-phenyl)-1-phenyl-3-propanedione is isolated (100°C). By treatment with 300 ml of acetic acid and 210 ml of hydrobromic acid, the expected product is obtained. Weight obtained: 61.2 g (Rdt: 54.7 %), PF,, = 210°C (toluene), IR: v c = 0 (pyrone): -1

1640 cm . RMN (CDCl3> 6 i ppm i. forhold til TMS, 2 H ved 5 (singlett), 1 H ved 7,1 (singlett), 7 H fra 7,3 til 8,3 (multiplett) . 1640 cm. NMR (CDCl3 > 6 in ppm in. relative to TMS, 2 H at 5 (singlet), 1 H at 7.1 (singlet), 7 H from 7.3 to 8.3 (multiplet).

Eksempel 15 Example 15

( Hy dr ok sy- 2- metoksytr. etyl- 3- metyl- 5- f enyl) - 1- etanon <C>11<H>14°3' PM = 194 • (Hy dr ok sy- 2- methoxytr. ethyl- 3- methyl- 5- phenyl) - 1- ethanone <C>11<H>14°3' PM = 194 •

Oppnådd i henhold til eksempel 2 ut fra (klormetyl-3-hydroksy-2-metyl-5-fenyl-l-etanon (PEQ 4rm= <1>10-116°C). Oppnådd vekt: 190,7 g (Rdt; 49 %), PE^ , : 95-l03°C, IR: vc = 0 (keton): Obtained according to example 2 from (chloromethyl-3-hydroxy-2-methyl-5-phenyl-l-ethanone (PEQ 4rm= <1>10-116°C). Obtained weight: 190.7 g (Rdt; 49%), PE^ , : 95-103°C, IR: vc = 0 (ketone):

. u, t> mm . u, t> mm

1650 cm . RMN (CC14) 5 i ppm i forhold til TMS. 3' H ved 1,8 (singlett), 3 H ved 2,1 (singlett), 3 H ved 2,9 (singlett), 2H ved 4 (singlett), 2 H fra 6,8 til 7 (massivt), 1 H ved 12,5 (utbyttbar med D20). 1650 cm. RMN (CC14) 5 in ppm relative to TMS. 3' H at 1.8 (singlet), 3 H at 2.1 (singlet), 3 H at 2.9 (singlet), 2H at 4 (singlet), 2 H from 6.8 to 7 (massive), 1 H at 12.5 (exchangeable with D20).

Eksempel 16 Example 16

Brom- metyl- 8- metyI- 6- f enyl- 2- 4H- [ 1- 3 - benzopyran- 4- on Bromo- methyl- 8- methyl- 6- phenyl- 2- 4H- [ 1- 3- benzopyran- 4- one

C1?H Br02, PM = 329,20. C 1 H BrO 2 , PM = 329.20.

Fremstilt i henhold til eksempel 3 ut fra 204 g (1,05 mol) Prepared according to example 3 from 204 g (1.05 mol)

(hydroksy-2-metoksymetyl-3-metyl-5-fenyl)-1-etanon og 210 g (1,4 mol) etylbenzoat. Etter isolering behandles den oppnådde olje med 520 ml eddiksyre og 410 ml 62% bromhydrogensyre. Oppnådd vekt: 108 g (Rdt: 31,2 %), PFR: 186°C (aceton), IR: v c = 0 (pyron): 1640 cm"<1.> RMN (DMSO) 6 i ppm i forhold til TMS, 3 H (hydroxy-2-methoxymethyl-3-methyl-5-phenyl)-1-ethanone and 210 g (1.4 mol) of ethyl benzoate. After isolation, the obtained oil is treated with 520 ml of acetic acid and 410 ml of 62% hydrobromic acid. Weight obtained: 108 g (Rdt: 31.2%), PFR: 186°C (acetone), IR: v c = 0 (pyrone): 1640 cm"<1.> RMN (DMSO) 6 in ppm relative to TMS , 3 H

ved 3,2 (singlett), 2 H ved 5 (singlett),- 1 H ved 7 (singlett), at 3.2 (singlet), 2 H at 5 (singlet), - 1 H at 7 (singlet),

7 H fra 7,3 til 8,3 (multiplett). 7 H from 7.3 to 8.3 (multiplet).

Eksempel 17 Example 17

Brom- metyl- 8-( tenyl- 2)- 2- 4H-[ 1]- benzopyran- 4- on Bromo- methyl- 8-(thenyl- 2)- 2- 4H-[ 1]- benzopyran- 4- one

C14HgBr2, PM = 321,2 C14HgBr2, MW = 321.2

Fremstilt i henhold til eksempel 3 ut fra 118 g (0,65 mol) Prepared according to example 3 from 118 g (0.65 mol)

(hydroksy-2-metoksyrnetyl-3-fenyl)-1-etanon og 127 g (0,82 mol) a-etyltenoat. Den oppnådde rå olje behandles med 450 ml av 62 % bromhydrogensyre og 600 ml eddiksyre, i henhold til eksempel 4, og man oppnår 80,1 g (Rdt: 40 %) av et fast stoff. PF: 174°C (etanol). IR: v c = 0 (pyron): 1640 cm<-1>. RMN (CDCl^) 6 i ppm (hydroxy-2-methoxymethyl-3-phenyl)-1-ethanone and 127 g (0.82 mol) α-ethyl thenoate. The obtained crude oil is treated with 450 ml of 62% hydrobromic acid and 600 ml of acetic acid, according to example 4, and 80.1 g (Rdt: 40%) of a solid is obtained. PF: 174°C (ethanol). IR: v c = 0 (pyrone): 1640 cm<-1>. NMR (CDCl 2 ) 6 in ppm

i forhold til TMS. 2 H ved 4,8 (singlett), 1 H ved 6,7 (singlett), 6 H fra 7,1 til -8,3 (multiplett). in relation to TMS. 2 H at 4.8 (singlet), 1 H at 6.7 (singlet), 6 H from 7.1 to -8.3 (multiplet).

Eksempel 18 Example 18

( Brom- metyl)- 8-( metoksy- 3- fenyl)- 2- 4H-[ 1]- benzopyranon- 4 C17H13<B>r03" PM = 345'20 ( Bromo-methyl)- 8-( methoxy- 3- phenyl)- 2- 4H-[ 1]- benzopyranone- 4 C17H13<B>r03" PM = 345'20

Fremstilt i henhold til eksempel 8 ut fra 57,1 g (.0,38 mol) Prepared according to Example 8 from 57.1 g (.0.38 mol)

(metoksy-3-fenyl)-1-etanon, og 120 g (0,571 mol) metyl-metoksy-2- metoksymetyl-3-benzoat. Oppnådd vekt; 49,8 g (Rdt: 38 %), (methoxy-3-phenyl)-1-ethanone, and 120 g (0.571 mol) methyl-methoxy-2-methoxymethyl-3-benzoate. Gained weight; 49.8 g (Rdt: 38%),

PFV = 160°C (toluen-heksan). IR: v c = 0 = 16 55 cm"<1.> RMN (CDC13), 3 H ved 3,95 (singlett), 2 H ved 4,8 (singlett), i H ved 6,8 (singlett), 6 H fra 7,0 til 7,9 (multiplett), 1 H ved 8,2 (dublet-t av dublett, = 8 Hz; J2 = 2 Hz). PFV = 160°C (toluene-hexane). IR: v c = 0 = 16 55 cm"<1.> RMN (CDC13), 3 H at 3.95 (singlet), 2 H at 4.8 (singlet), i H at 6.8 (singlet), 6 H from 7.0 to 7.9 (multiplet), 1 H at 8.2 (doublet-t of doublet, = 8 Hz; J2 = 2 Hz).

Eksempel 19 Example 19

Hydroksy- 3- metyl- 8- fenyl- 2- 4H- [ 1]- benzopyranon- 4 Hydroxy- 3- methyl- 8- phenyl- 2- 4H- [ 1]- benzopyranone- 4

<C>16<H>12°3' PM = 252 ' 21' <C>16<H>12°3' PM = 252 ' 21'

Til'en løsning av 90,1 g (0,6 mol) av (hydroksy-2-metyl-3- fenyl)-1-etanon og 63,7 g (0,6 mol) benzaldehyd i 1,2 liter etanol tilsetter man ved lavere temperatur enn 30°C en løsning av 81,6 g (2,04 mol) av natriumhydroksydpastiller i 163 ml vann. Man rører en natt ved omgivelsestemperatur og tilsetter så 204ml av en 20 % vandig natriumhydroksydløsning, fortynnet med 4 1 etanol. Man avkjøler på isbad og tilsetter hurtig 825 ml av en 15 % oksygenert vannløsning. Man rører i 4 timer ved 25°C og surgjør så med 30 % I^SO^, og man tømmer dette på en vann/is-blanding (15 1). Man lar dette hvile en natt, og man filtrerer det oppnådde utfel1ingsprodukt som man rekrystalliserer i toluen. To a solution of 90.1 g (0.6 mol) of (hydroxy-2-methyl-3-phenyl)-1-ethanone and 63.7 g (0.6 mol) benzaldehyde in 1.2 liters of ethanol add at a temperature lower than 30°C, a solution of 81.6 g (2.04 mol) of sodium hydroxide lozenges in 163 ml of water. The mixture is stirred overnight at ambient temperature and then 204 ml of a 20% aqueous sodium hydroxide solution, diluted with 4 1 ethanol, is added. Cool in an ice bath and quickly add 825 ml of a 15% oxygenated water solution. It is stirred for 4 hours at 25°C and then acidified with 30% I^SO^, and this is poured onto a water/ice mixture (15 1). This is allowed to rest overnight, and the precipitation product obtained is filtered and recrystallized in toluene.

Oppnådd vekt: 18,3 g (Rdt: 12 .%). PFV = 180 C. IR: v OH = Achieved weight: 18.3 g (Rdt: 12 .%). PFV = 180 C. IR: v OH =

-1 -1 -1 3300 cm , v c = 0 (pyron) = 1625 cm (skulder ved 1640 cm , RMN (CDC13), 3 H ved 2,66 (singlett), 1 H ved 6,7 (utbyttbar med D20), 5 H fra 7,2 til 7,7 (multiplett), 3 H fra 8,0 til 8,5 (multiplett). -1 -1 -1 3300 cm , v c = 0 (pyron) = 1625 cm (shoulder at 1640 cm , RMN (CDC13), 3 H at 2.66 (singlet), 1 H at 6.7 (exchangeable with D20) , 5 H from 7.2 to 7.7 (multiplet), 3 H from 8.0 to 8.5 (multiplet).

Eksempel 20 Example 20

Metoksy- 3- metyl- 8- fenyl- 2- 4H-[ 1]- benzopyranon- 4 Methoxy- 3- methyl- 8- phenyl- 2- 4H-[ 1]- benzopyranone- 4

C17<H>14°3* PM = 266'30 C17<H>14°3* PM = 266'30

Man oppvarmer under tilbakeløpskjøling i 16 timer en blanding av 18 g (0,071 mol) '. hydroksy-3-metyl-8-fenyl-2-4H- [1] -benzopyranon-4 , 9,86 g (0,071 mol) kaliumkarbonat, 100 ml aceton og 9,9 g (0,078 mol) dimetylsulfat. Så filtrerer man varmt, avkjø-ler filtratet, filtrerer det oppnådde utfellingsprodukt og rekrystalliserer dette i aceton. Oppnådd vekt: 14,5 g (Rdt: 76%). PFR = 143°C. IR: v c = 0 (pyron) = 1645 cm"<1>. RMN (CDCl^), 3 H ved 2,6 (singlett), 3 H ved 3,97 (singlett), 5 H fra 7,1 til 7,7 (multiplett), 3 H fra 7,9 til 8,4 (multiplett). A mixture of 18 g (0.071 mol) is heated under reflux for 16 hours. hydroxy-3-methyl-8-phenyl-2-4H-[1]-benzopyranone-4, 9.86 g (0.071 mol) of potassium carbonate, 100 ml of acetone and 9.9 g (0.078 mol) of dimethyl sulfate. You then filter hot, cool the filtrate, filter the precipitation product obtained and recrystallize this in acetone. Achieved weight: 14.5 g (Rdt: 76%). PFR = 143°C. IR: v c = 0 (pyrone) = 1645 cm"<1>. RMN (CDCl^), 3 H at 2.6 (singlet), 3 H at 3.97 (singlet), 5 H from 7.1 to 7 .7 (multiplet), 3 H from 7.9 to 8.4 (multiplet).

Eksempel 21 Example 21

( Brom- metyl)- 8- metoksy- 3- fenyl- 2- 4H-[ 1]- benzopyranon- 4 C17H]3Br03. PM = 34 5,20. ( Bromo-methyl)- 8- methoxy- 3- phenyl- 2- 4H-[ 1]- benzopyranone- 4C17H]3Br03. PM = 34 5.20.

Man oppvarmer under tilbakeløp i 8 timer under ultrafio-lett bestråling en blanding av 11 g (0,041 mol) av metoksy-3-metyl-8-fenyl-2-4H-[1]-benzopyranon-4, 8,03 g (0,045 mol) av N-bromsuksinimid, 350 ml karbontetraklorid og 0,2 g azobis-isobutyronitril. Man filtrerer varmt, lar filtratet henstå en natt i kjøleskap. Man filtrerer, vasker med vann og rekrystalliserer i etylacetat. Oppnådd vekt: 6,2 (Rdt: 43 %). PFV = 157°C. A mixture of 11 g (0.041 mol) of methoxy-3-methyl-8-phenyl-2-4H-[1]-benzopyranone-4, 8.03 g (0.045 mol) of N-bromosuccinimide, 350 ml of carbon tetrachloride and 0.2 g of azobis-isobutyronitrile. You filter hot, leave the filtrate overnight in a refrigerator. Filter, wash with water and recrystallize in ethyl acetate. Achieved weight: 6.2 (Rdt: 43%). PFV = 157°C.

-1 -1

IR: v c = 0 : 1630 cm . RMN (CDCl-j) 3 H ved 3,95 (singlett), IR: v c = 0 : 1630 cm . NMR (CDCl-j) 3 H at 3.95 (singlet),

2 H ved 4,83 (singlett), 5 H fra 7,2 til 7,9 (multiplett), 3 H fra 0,1 til 8,5 (multiplett). 2 H at 4.83 (singlet), 5 H from 7.2 to 7.9 (multiplet), 3 H from 0.1 to 8.5 (multiplet).

Eksempel 22 Example 22

( Klormetyl- 3- hydroksy- 2- metoksy- 5- fenyl)- 1- etanon ( Chloromethyl- 3- hydroxy- 2- methoxy- 5- phenyl)- 1- ethanone

<C1>0<H>llCl03' PM = 214,65. <C1>0<H>11Cl03' PM = 214.65.

Man oppvarmer i 7 timer ved 50°C en blanding av 47 g (0,283 mol) av (hydroksy-2-metoksy-5-fenyl)-1-etanon, 8,5 g (0,283 mol) av polyoksymetylen og 215 ml konsentrert saltsyre. Etter avkjøling tar man opp i benzen, filtrerer et uløselig ma-teriale, vasker til nøytralitet, fordamper benzenet under vakuum og rekrystalliserer det oppnådde faststoff i heksan, Oppnådd vekt: 37,1 g (Rdt: 61 %). PF„ = 71°C. IR: v c = 0 = 1650 cm"<1 >RMN. (CDC13), 3 H ved 2,63 (singlett), 3 H ved 3,85 (singlett), A mixture of 47 g (0.283 mol) of (hydroxy-2-methoxy-5-phenyl)-1-ethanone, 8.5 g (0.283 mol) of polyoxymethylene and 215 ml of concentrated hydrochloric acid is heated for 7 hours at 50°C . After cooling, take up in benzene, filter an insoluble material, wash to neutrality, evaporate the benzene under vacuum and recrystallize the obtained solid in hexane, Weight obtained: 37.1 g (Rdt: 61%). PF„ = 71°C. IR: v c = 0 = 1650 cm"<1 >RMN. (CDC13), 3 H at 2.63 (singlet), 3 H at 3.85 (singlet),

2 H ved 4,7 (singlett), 2 H fra 7,2 til 7,4 (multiplett), 1 H 2 H at 4.7 (singlet), 2 H from 7.2 to 7.4 (multiplet), 1 H

ved 12,6 (singlett). at 12.6 (singlet).

Eksempel 23 Example 23

( Hydroksy- 2- metoksy- 5- metoksymetyl- 3- fenyl)- 1- etanon C11H14°4' PM = 210'23 ( Hydroxy- 2- methoxy- 5- methoxymethyl- 3- phenyl)- 1- ethanone C11H14°4' PM = 210'23

Fremstilt i henhold til eksempel 2 ut fra 36,8 g (0,171 mol) av (klormetyl-3-hydroksy-2-metoksy-5-fenyl)-1-etanon. ' Oppnådd vekt: 24,7 g (Rdt: 69 %). PEn - mm ~ 110-114°C. IR: v c = 0 = Prepared according to example 2 from 36.8 g (0.171 mol) of (chloromethyl-3-hydroxy-2-methoxy-5-phenyl)-1-ethanone. ' Weight achieved: 24.7 g (Rdt: 69 %). PEn - mm ~ 110-114°C. IR: v c = 0 =

0,3 mm Hg _, 0.3 mm Hg _,

1650 cm" , v OH = 3000'.til 3600 cm . RMN. (CDC13>, 3 H ved 1650 cm" , v OH = 3000'. to 3600 cm . RMN. (CDC13 >, 3 H at

.2,57 (singlett), 3 H ved 3,42 (singlett), 3 H ved 3,77 (singlett), 2 H ved 4,5 (singlett), 1 H ved 7,1 (dublett, J = 3 Hz), 1 H ved 7,25 (dublett, J = 3 Hz), 1 H ved 12,0 (singlett). .2.57 (singlet), 3 H at 3.42 (singlet), 3 H at 3.77 (singlet), 2 H at 4.5 (singlet), 1 H at 7.1 (doublet, J = 3 Hz), 1 H at 7.25 (doublet, J = 3 Hz), 1 H at 12.0 (singlet).

Eksempel 24 Example 24

( Hydroksy- 2- metoksy- 5- metoksyrnety1- 3- fenyl)- 1- fenyl- 3- propandion-1, 3 <-><C>18<H>18<0>5<-> PM = 314,34. ( Hydroxy- 2- methoxy- 5- methoxyrnethy1- 3- phenyl)- 1- phenyl- 3- propanedione-1, 3 <-><C>18<H>18<0>5<-> PM = 314.34 .

Man vasker tre ganger heksan (81,6 g (1,7 mol) av en 50% suspensjon av natriumhydrid i olje. Man anbringer hydridet i suspensjon i 600 ml vannfritt dioksan, oppvarmer til 80°C og tilsetter dråpevis i løpet av 1 time og 30 minutter en løsning av 114 g (0,542 mol) av (hydroksy-2-metoksy-5-metoksymety1-3-fenyl)— 1-etanon og 122 g (0,813 mol) etylbenzoat i 150 mi vannfritt dioksan. Man oppvarmer så i 3 timer ved 80°C, avkjøler, fortynner med 3,5 1 heksan, filtrerer, vasker faststoffet med heksan. Så tilsetter man dette faststoff i porsjoner til en blanding som om-røres.energisk, av 1 liter vann, 1 liter eddiksyre og 1,5 liter kloroform. Man dekanterer, ekstraherer med kloroform, vasker til nøytralitet, tørker og inndamper under-vakuum. Man oppnår 200 g av en olje som anvendes uten ytterligere rensning i det følgende trinn. A 50% suspension of sodium hydride in oil is washed three times with hexane (81.6 g (1.7 mol)). The hydride is suspended in 600 ml of anhydrous dioxane, heated to 80°C and added dropwise over the course of 1 hour and 30 minutes a solution of 114 g (0.542 mol) of (hydroxy-2-methoxy-5-methoxymethyl-3-phenyl)-1-ethanone and 122 g (0.813 mol) ethyl benzoate in 150 ml of anhydrous dioxane. It is then heated in 3 hours at 80°C, cool, dilute with 3.5 L of hexane, filter, wash the solid with hexane, then add this solid in portions to a vigorously stirred mixture of 1 liter of water, 1 liter of acetic acid and 1.5 liters of chloroform. One decants, extracts with chloroform, washes to neutrality, dries and evaporates under vacuum. One obtains 200 g of an oil which is used without further purification in the following step.

Eksempel 25 Example 25

( Brom- metyl- 8- metoksy- 6- fenyl- 2- 4H-[ 1]- benzopyranon- 4 C17H13Br03 . PM = 345,20. (Bromo-methyl-8-methoxy-6-phenyl-2-4H-[1]-benzopyranone-4C17H13Br03. PM = 345.20.

'Fremstilt i henhold til eksempel 4 ut fra (hydroksy-2-metoksy-5-metoksy-metyl-3-fenyl)-1-fenyl-3-propandion-l,3 som 'Prepared according to example 4 from (hydroxy-2-methoxy-5-methoxy-methyl-3-phenyl)-1-phenyl-3-propanedione-1,3 which

er oppnådd som angitt ovenfor. Oppnådd vekt: 112,8 g (Rdt glo-bal; 60 %). PFK = 194°C. IR: v c = 0 (pyron) = 1650 cm"<1>. is obtained as indicated above. Achieved weight: 112.8 g (Rdt glo-bal; 60%). PFK = 194°C. IR: v c = 0 (pyron) = 1650 cm"<1>.

RMN (DMSO), 3 H ved 3,9 (singlett), 2 H ved 5,1 (singlett), 8 H fra 7,0 til 8,3 (multiplett). NMR (DMSO), 3 H at 3.9 (singlet), 2 H at 5.1 (singlet), 8 H from 7.0 to 8.3 (multiplet).

Eksempel 2 6 Example 2 6

( Brom- metyl)- 8-( dimetoksy- 3, 4- fenyl)- 2- 4H-[ 1]- benzopyranon- 4 ClgH15Br04. PM = 375,23. (Bromo-methyl)- 8-(dimethoxy-3,4-phenyl)-2-4H-[1]-benzopyranone-4ClgH15Br04. PM = 375.23.

Fremstilt i henhold til eksempel 8 ut fra 68,6 g (0,38 mol) av (dimetoksy-3,4-fenyl)-1-etanon og 120 g (0,571 mol) av metyl-metoksy-2-metoksymetyl-3-benzoat. Oppnådd vekt: 82 g (Rdt: 57 %). PFV = 185°C (toluen/heksan). IR: v c = 0 (pyron) = 1630 cm"<1. >RMN (CDCl-j) , 3 H ved 3,97 (singlett), 3 H ved 4,0 (singlett), 2 H ved 4,8 (singlett), 1 H ved 6,8 (singlett), 5 H fra 6,9 til 7,9 (multiplett), 1 H ved 8,22 (dublett av dublett, JJL = 8. Hz; J2 = 2 Hz). Prepared according to Example 8 from 68.6 g (0.38 mol) of (dimethoxy-3,4-phenyl)-1-ethanone and 120 g (0.571 mol) of methyl-methoxy-2-methoxymethyl-3- benzoate. Achieved weight: 82 g (Rdt: 57%). PFV = 185°C (toluene/hexane). IR: v c = 0 (pyrone) = 1630 cm"<1. >RMN (CDCl-j) , 3 H at 3.97 (singlet), 3 H at 4.0 (singlet), 2 H at 4.8 ( singlet), 1 H at 6.8 (singlet), 5 H from 6.9 to 7.9 (multiplet), 1 H at 8.22 (doublet of doublet, JJL = 8. Hz; J2 = 2 Hz).

Eksempel 2 7 Example 2 7

Difenyl- 2, 3- metyl- 8- 4H-[ 1]- benzopyranon- 4 Diphenyl- 2, 3- methyl- 8- 4H-[ 1]- benzopyranone- 4

<C>22<H>16°2<-> PM = 312'37- <C>22<H>16°2<-> PM = 312'37-

Man oppvarmer i 7 h mellom 170 og 180°C en blanding av 98g (0,433 mol) (hydroksy-2-metyl-3-fenyl)-1-feny1-2-etanon, 98 g (0,433 mel) benzosyreanhydrid og 62,4 g (0,433 mol) natriumbenz-oat. Man avkjøler, tar opp i benzen, vasker med vann og deretter med en vandig løsning av bikarbonat, og så med vann. Man fordamper benzenet under vakuum og rekrystalliserer det oppnådde produkt i toluen. Oppnådd vekt: 36,4 g (Rdt: 27 %) . PF^, = 209-2lO°C. IR: v c- 0 = 1630 cm"<1>. RMN (CDCl3> , 3 H ved 2,55 (singlett), 12 H fra 7,1 til 7,7 (multiplett), 1 H ved 8,5 (dublett av dublett, J =8 Hz;J2 = 2 Hz) . A mixture of 98 g (0.433 mol) (hydroxy-2-methyl-3-phenyl)-1-phenyl-2-ethanone, 98 g (0.433 mol) benzoic anhydride and 62.4 g (0.433 mol) of sodium benzoate. It is cooled, taken up in benzene, washed with water and then with an aqueous solution of bicarbonate, and then with water. The benzene is evaporated under vacuum and the product obtained is recrystallized in toluene. Achieved weight: 36.4 g (Rdt: 27%) . PF^, = 209-210°C. IR: v c- 0 = 1630 cm"<1>. RMN (CDCl3> , 3 H at 2.55 (singlet), 12 H from 7.1 to 7.7 (multiplet), 1 H at 8.5 ( doublet of doublet, J =8 Hz;J2 = 2 Hz) .

Eksempel 28 Example 28

Brom- metyl- 8- difenyl- 2 , 3- 4H- [ 1] - b. enzopyranon- 4 Bromo- methyl- 8- diphenyl- 2 , 3- 4H- [ 1] - b. enzopyranone- 4

<C>22<H>15<B>r02* PM = 391 ' 21' <C>22<H>15<B>r02* PM = 391 ' 21'

Fremstilt i henhold til eksempel 21 ut fra 36 g (0,115 mol) av difenyl-2,3-metyl-8-4H-[1]-benzopyranon-4. Etter filt-rering av suksinimidet inndampes filtratet under vakuum, det oppnådde faststoff tas opp i vann og filtreres. Oppnådd vekt: 45 g (Rdt kvantitativt). PF,. = 14 3-14 7°C. IR: •.• c = 0 (pyron) Prepared according to Example 21 from 36 g (0.115 mol) of diphenyl-2,3-methyl-8-4H-[1]-benzopyranone-4. After filtering the succinimide, the filtrate is evaporated under vacuum, the solid obtained is taken up in water and filtered. Achieved weight: 45 g (Rdt quantitative). PF,. = 14 3-14 7°C. IR: •.• c = 0 (pyrone)

-1 -1

= 1635 cm . RMN (CDC13>, 2 H ved 4,8 (singlett), 12 H fra 7 = 1635 cm. NMR (CDC13>, 2 H at 4.8 (singlet), 12 H from 7

til 7,9 (multiplett), 1 H ved 8,25 (dublett av dublett), J = 8 Hz, J2 = 2 Hz). to 7.9 (multiplet), 1 H at 8.25 (doublet of doublet), J = 8 Hz, J2 = 2 Hz).

Eksempel 2 9 Example 2 9

Brom- metyl- 8-( naftyl- 2)- 2- 4H-[ 1]- benzopyranon- 4 Bromo- methyl- 8-( naphthyl- 2)- 2- 4H-[ 1]- benzopyranone- 4

<C>20<H>13Br03' PM = 362'22- <C>20<H>13Br03' PM = 362'22-

Fremstilt i henhold til eksempel 8 ut fra 105,1 g (0,5 mol) av metyl-metoksy-2-metoksymetyl-3-benzpat og 85,1 g (0,5 mol) av (naftyl-2)-2-etanon. Etter isolering tas den oppnådde rå ol-je opp i 600 ml eddiksyre og 526 ml av 62 % bromhydrogensyre. Ved behandling i henhold til den vanlige metode oppnår man 61 g (Rdt: 30 %) PF„ = 190-192°C (toluen). IR: v c = 0 (pyron) = -1 Prepared according to Example 8 from 105.1 g (0.5 mol) of methyl-methoxy-2-methoxymethyl-3-benzpate and 85.1 g (0.5 mol) of (naphthyl-2)-2- ethane. After isolation, the obtained crude oil is taken up in 600 ml of acetic acid and 526 ml of 62% hydrobromic acid. Treatment according to the usual method yields 61 g (Rdt: 30%) PF„ = 190-192°C (toluene). IR: v c = 0 (pyrone) = -1

1650 cm 1650 cm

Eksempel 30 Example 30

Brom- metyl- 8-( furyl- 2)- 2- 4H [ 1]- benzopyranon- 4 Bromo- methyl- 8-(furyl- 2)- 2- 4H [ 1]- benzopyranone- 4

C14HgBr03. PM = 305,13. C14HgBr03. PM = 305.13.

Fremstilt i henhold til eksempel 8 ut fra 105,1 g (0,5 mol) av metyl-metoksy-2-metoksymetyl-3-benzoat og 55 g (0,5 mol) av furyl-2)-1-etanon. Etter isolering av den rå olje tas denne opp med 600 ml eddiksyre og 4 26 ml av 62 % bromhydrogensyre. Ved behandling i henhold til den vanlige metode oppnår man 23,4g (Rdt: 15 %) . PFK,, = 210°C. IR: v c = 0 (pyron) 1660 cm"<1.>Prepared according to example 8 from 105.1 g (0.5 mol) of methyl-methoxy-2-methoxymethyl-3-benzoate and 55 g (0.5 mol) of furyl-2)-1-ethanone. After isolation of the crude oil, this is taken up with 600 ml of acetic acid and 4 26 ml of 62% hydrobromic acid. When treated according to the usual method, 23.4g (Rdt: 15%) is obtained. PFK,, = 210°C. IR: v c = 0 (pyron) 1660 cm"<1.>

Eksempel 31 Example 31

Cykloheksyl- 1-( hydroksy- 2- metoksymetyl- 3- fenyl)- 3- propandion- l, 3 C17H2204.. PM = 290,36. Cyclohexyl-1-(hydroxy-2-methoxymethyl-3-phenyl)-3-propanedione-1,3 C17H22O4.. PM = 290.36.

Fremstilt i henhold til eksempel 24 ut fra 53,3 g (0,296 mol) av (hydroksy-2-metoksymetyl-3-fenyl)-1-etanon og 92,4 g (0,59 mol) av etyl-cykloheksylkarboksylat, men ved å oppvarme 3 H ved til-bakeløpsk jøling ( istedenfor 3 H ved 80°C og ved å destillere den oppnådde olje etter den endelige inndampning. Oppnådd vekt: Prepared according to Example 24 from 53.3 g (0.296 mol) of (hydroxy-2-methoxymethyl-3-phenyl)-1-ethanone and 92.4 g (0.59 mol) of ethyl cyclohexyl carboxylate, but at to heat 3 H by refluxing (instead of 3 H at 80°C and by distilling the obtained oil after the final evaporation. Weight obtained:

18 g (Rdt: 21 %) . PE^ mm Hg = 140-180°C. 18 g (Rdt: 21%) . PE^ mm Hg = 140-180°C.

Eksempel 32 Example 32

Brom- metyl- 8- cykloheksyl- 2- 4H- LI]- benzopyranon- 4 Bromo- methyl- 8- cyclohexyl- 2- 4H- LI]- benzopyranone- 4

<C>1(,<H>17Br02. PM = 321,22. <C>1(,<H>17BrO2. PM = 321.22.

Fremstilt i henhold til eksempel 4 ut fra 18 g (0,062 mol) av cykloheksyl-1-(hydroksy-2-metoksymetyl-3-fenyl)-3-propandion-1,3. Oppnådd vekt: 15,2 g (Rdt: 76 %). PF = 130°C Prepared according to example 4 from 18 g (0.062 mol) of cyclohexyl-1-(hydroxy-2-methoxymethyl-3-phenyl)-3-propanedione-1,3. Weight achieved: 15.2 g (Rdt: 76%). PF = 130°C

(aceton). IR: v c = 0 (pyron) = 1645 cm"<1.> RMN (CDC13), (acetone). IR: v c = 0 (pyrone) = 1645 cm"<1.> RMN (CDC13),

11 H fra 1,1 til 3,0 (multiplett), 2 H ved 4,7 (singlett), 1 H ved 6,2 (singlett), 1 H ved 7,3 (triplett, J = 8 Hz), 1 H ved 7,65 (dublett av dublett, ^ = 8 Hz, J2 = 2 Hz)., 1 H ved 8,15 (dublett av dublett, J1 = 8 Hz, J2 = 2 Hz). 11 H from 1.1 to 3.0 (multiplet), 2 H at 4.7 (singlet), 1 H at 6.2 (singlet), 1 H at 7.3 (triplet, J = 8 Hz), 1 H at 7.65 (doublet of doublet, ^ = 8 Hz, J2 = 2 Hz)., 1 H at 8.15 (doublet of doublet, J1 = 8 Hz, J2 = 2 Hz).

Eksempel 33 Example 33

( Hydroksy- 2- metyl- 3- fenyl)- 1- fenyl- 2- etanon ( Hydroxy- 2- methyl- 3- phenyl)- 1- phenyl- 2- ethanone

C1<5H>14°2' PM = 226 ,28. C1<5H>14°2' PM = 226.28.

Man oppvarmer i 16 timer under tilbakeløpskjøling en løs-ning av 126 g (0,5 mol) av hydroksy-4-metyl-8-fenyl-3-2H-[1]-benzopyranon-2 (C. Mentzer m.fl., Bull. Soc.Chim. France 1949 749) og 100 g (2,5 mol), natriumhydroksyd i 1 liter vann. Man tømmer så på en blanding av 6 N HCl og is, og man filtrerer det oppnådde utfellingsprodukt. Oppnådd vekt: 91 g. PF^ = 44°C. IR: v c = 1630 cm"<1,> v OH = 2700 til 3500 cm"<1.> RMN (CDC13), 3 H ved 2,24 (singlett) 2 H ved 4,24 (singlett), 1 H ved 6,8 (triplett, J = 8 Hz), 6 H fra 7,2 til 7,6 (multiplett), 1 H ved 7,76 (dublett, J = 8 Hz), 1 H ved 15,6 (utbyttbar med D20). A solution of 126 g (0.5 mol) of hydroxy-4-methyl-8-phenyl-3-2H-[1]-benzopyranone-2 (C. Mentzer et al.) is heated for 16 hours under reflux. , Bull. Soc. Chim. France 1949 749) and 100 g (2.5 mol), sodium hydroxide in 1 liter of water. A mixture of 6 N HCl and ice is then emptied, and the precipitation product obtained is filtered. Weight achieved: 91 g. PF^ = 44°C. IR: v c = 1630 cm"<1,> v OH = 2700 to 3500 cm"<1.> RMN (CDC13), 3 H at 2.24 (singlet) 2 H at 4.24 (singlet), 1 H at 6.8 (triplet, J = 8 Hz), 6 H from 7.2 to 7.6 (multiplet), 1 H at 7.76 (doublet, J = 8 Hz), 1 H at 15.6 (interchangeable with D20).

Eksempel 34 Example 34

Metyl- 8- fenyl- 3- 4H-[ 13- benzopyranon- 4 Methyl- 8- phenyl- 3- 4H-[ 13- benzopyranone- 4

<C>16<n>i2°2-" PM = 236 '77- <C>16<n>i2°2-" PM = 236 '77-

Man oppvarmer i 8 H en blanding av 85 g' (0,375 mol) av hydroksy-2-metyl-3-fenyl)-1-fenyl-2-etanon, 500 ml pyridin, A mixture of 85 g' (0.375 mol) of hydroxy-2-methyl-3-phenyl)-1-phenyl-2-ethanone, 500 ml of pyridine,

50 ml piperidin og 810 ml trietylortoformiat. Så tømmer man dette ned i en blanding av 6N saltsyre og is (3 liter). Man filtrerer det oppnådde utfellingsprodukt og rekrystalliserer i isopropanol. Oppnådd vekt; 80,9 g (Rdt: 91 %). PF„ = 110-111°C 50 ml of piperidine and 810 ml of triethyl orthoformate. This is then emptied into a mixture of 6N hydrochloric acid and ice (3 litres). The precipitation product obtained is filtered and recrystallized in isopropanol. Gained weight; 80.9 g (Rdt: 91%). PF„ = 110-111°C

-1 -1

IR: v c = 0 = 1650 cm . RMN (CDCl3), 3 H ved 2,5 (singlett), IR: v c = 0 = 1650 cm . NMR (CDCl3), 3 H at 2.5 (singlet),

7 H fra 7,1 til 7,8 (multiplett), 1 H ved 8,02 (singlett), 1 H ved 2,2 (dublett av dublett, J1 = 8 Hz, J2 = 2 Hz). 7 H from 7.1 to 7.8 (multiplet), 1 H at 8.02 (singlet), 1 H at 2.2 (doublet of doublet, J1 = 8 Hz, J2 = 2 Hz).

Eksempel 3 5 Example 3 5

Brom- rnetyl- 8- f enyl- 3- 4H- [ 1] - benzopyranon- 4 Bromo- nethyl- 8- phenyl- 3- 4H- [ 1] - benzopyranone- 4

C16HllBr02* PM = 315'17- C16HllBr02* PM = 315'17-

Fremstilt i henhold til eksempel 21 Ut fra 80,9 g (0,34 mol) av metyl-8-fenyl-3-4H-[1]-benzopyranon-4 og 73,4 g (0,41 mol) av N-bromsuksinimid. Oppnådd vekt: 88,2 g (Rdt: 82 %). PFK = 142°C (etylacetat). IR: v c = 0. (pyron) = 1640 cm"<1>. Prepared according to Example 21 From 80.9 g (0.34 mol) of methyl-8-phenyl-3-4H-[1]-benzopyranone-4 and 73.4 g (0.41 mol) of N- bromosuccinimide. Achieved weight: 88.2 g (Rdt: 82%). PFK = 142°C (ethyl acetate). IR: v c = 0. (pyron) = 1640 cm"<1>.

RMN (CDC13), 2 H ved 4,8 (singlett), 7 H fra 7,2 til 8,0 (multiplett), 1 H ved 8,18 (singlett), 1 H ved 8,4 (dublett av dublett, J1 = 8 Hz, J2 = 2 Hz). NMR (CDC13), 2 H at 4.8 (singlet), 7 H from 7.2 to 8.0 (multiplet), 1 H at 8.18 (singlet), 1 H at 8.4 (doublet of doublet, J1 = 8 Hz, J2 = 2 Hz).

Eksempel 36 Example 36

Metoksy- 2- metoksymetyl- 3- benzosyre Methoxy- 2- methoxymethyl- 3- benzoic acid

C10H12°4 * PM = 196 , 20' C10H12°4 * PM = 196 , 20'

Til en løsning av 315,3 g (1,5 mol) av metyl-metoksy-2-metoksymetyl-3-benzoat i 1,2 1 metanol tilsetter man en løsning av 118,8 g (1,8 mol) kaliumhydroksydpastiller i 300 ml vann, og man oppvarmer under tilbakeløpskjøling i 3 h. Så fordamper man metanolen under vakuum, fortynner med vann og vasker med eter. Vannfasen avkjøles, surgjøres med 6N HC1, ekstraheres med eter. Eterfasen vaskes med vann, tørkes, inndampes under vakuum, og det oppnådde faststoff rekrystalliseres i cykloheksan. Oppnådd vekt: 278 ,3 g (Rdt: 94 %) . PF^, = 68-6 9°C..IR: v c = 0 (syre) = 1700 cm"1. RMN (CDC13), 3 H ved 3,47 (singlett), 3 H ved 3,97 (singlett), 2 H ved 4,6 (singlett), 1 H ved 7,23 (triplett, J = A solution of 118.8 g (1.8 mol) potassium hydroxide lozenges in 300 ml of water, and heated under reflux for 3 h. The methanol is then evaporated under vacuum, diluted with water and washed with ether. The aqueous phase is cooled, acidified with 6N HCl, extracted with ether. The ether phase is washed with water, dried, evaporated under vacuum, and the solid obtained is recrystallized in cyclohexane. Achieved weight: 278.3 g (Rdt: 94 %). PF^, = 68-6 9°C..IR: v c = 0 (acid) = 1700 cm"1. NMR (CDCl 3 ), 3 H at 3.47 (singlet), 3 H at 3.97 (singlet) , 2 H at 4.6 (singlet), 1 H at 7.23 (triplet, J =

8 Hz), 1 H ved 7,7 (dublett av dublett, J = 8 Hz, J2 = 2 Hz), 8 Hz), 1 H at 7.7 (doublet of doublet, J = 8 Hz, J2 = 2 Hz),

1 H ved 8,05 (dublett av dublett, J1 = 8 Hz, J2 = 2 Hz). 1 H at 8.05 (doublet of doublet, J1 = 8 Hz, J2 = 2 Hz).

Eksempel 3 7 Example 3 7

( Metoksy- 2- metok symety1- 3- fenyl)- 1- etanon ( Methoxy- 2- methoxymethyl- 3- phenyl)- 1- ethanone

C11H14°3 * PM = 194 ,23 * C11H14°3 * PM = 194 .23 *

Til en løsning av 264,9 g (1,35 mol) metoksy-2-metoksymetyl-3-benzosyre i 1,35 1 kloroform og 2,7 ml DMF tilsetter man i en tynn stråle 148,5 ml (2,02 mol) tionyiklorid og oppvarmer så pro-gressivt til tilbakeløpstemperatur ved å regulere oppvarmningen på gassutslippet, og man holder tilbakeløpskjølingen vedlike i 2 timer. Så avkjøler man, inndamper under vakuum kloroformen og overskuddet av tionylkloridet og tar opp det oppnådde metoksy-2-metoksymetyl-3-benzosyreklorid med 270 ml vannfri eter. Man tilsetter denne løsning dråpevis til en løsning under tilbake-løp av 1,62 mol etyl-etoksymagnesiummalonat (fremstilt i henhold til Org.Syn.Coll.Vol.IV, s.708), og man oppvarmer i 3 h under tilbakeløp. Så avkjøler man på isbad, hydrolyserer med 5 % W^ SO^ til oppnåelse av to klare faser, dekanterer, ekstraherer med eter, vasker med vann og inndamper under vakuum. Inndampnings-re.sten tas opp med 460 ml eddiksyre, 300 ml vann og 58 ml konsentrert svovelsyre, og dette oppvarmes under tilbakeløp i 4 timer. Etter avkjøling ekstraherer man med eter. Vannfasen av-kjøles på isbad og gjøres alkalisk med 10 % NaOH, hvoretter man ekstraherer med eter. Eterfåsene forenes og vaskes med en vandig løsning av natriumbikarbonat og deretter med vann, tørkes og inndampes under vakuum. Inndampningsresten destilleres. Oppnådd vekt: 173,3 g (Rdt = 66 %) .■ PE_ . m„ = 100-105°C. IR: v c = 148.5 ml (2.02 mol ) thionium chloride and then progressively heats to reflux temperature by regulating the heating of the gas discharge, and the reflux cooling is maintained for 2 hours. It is then cooled, the chloroform and the excess thionyl chloride are evaporated under vacuum and the methoxy-2-methoxymethyl-3-benzoic acid chloride obtained is taken up with 270 ml of anhydrous ether. This solution is added dropwise to a refluxing solution of 1.62 mol of ethyl ethoxymagnesium malonate (prepared according to Org.Syn.Coll.Vol.IV, p.708), and heated for 3 hours under reflux. It is then cooled in an ice bath, hydrolyzed with 5% W^SO^ to obtain two clear phases, decanted, extracted with ether, washed with water and evaporated under vacuum. The evaporation residue is taken up with 460 ml of acetic acid, 300 ml of water and 58 ml of concentrated sulfuric acid, and this is heated under reflux for 4 hours. After cooling, extract with ether. The water phase is cooled in an ice bath and made alkaline with 10% NaOH, after which it is extracted with ether. The ether fractions are combined and washed with an aqueous solution of sodium bicarbonate and then with water, dried and evaporated under vacuum. The evaporation residue is distilled. Weight achieved: 173.3 g (Rdt = 66%) .■ PE_ . m„ = 100-105°C. IR: v c =

. 0,4 mmHg . 0.4mmHg

0 = 1690 cm" . RMN (CDC13), 3 H ved 2,63 (singlett), 3 H ved 3,5 (singlett), 3 H ved 3,8 (singlett), 2 H ved 4,55 (singlett), 4 H fra 7,0 til 7,8 (multiplett). 0 = 1690 cm". NMR (CDC13), 3 H at 2.63 (singlet), 3 H at 3.5 (singlet), 3 H at 3.8 (singlet), 2 H at 4.55 (singlet) , 4 H from 7.0 to 7.8 (multiplet).

Eksempel 38 Example 38

( Metoksy- 2- metoksymetyl- 3- fenyl)- 1- butandion- 1, 3 ( Methoxy- 2- methoxymethyl- 3- phenyl)- 1- butanedione- 1, 3

<C>13<H>16°4" PM = 236'27-<C>13<H>16°4" PM = 236'27-

Fremstilt i henhold til eksempel 24 ut fra 0,8 mol natriumhydrid, 77,77 g (0,4 mol) av (metoksymetyl-3-fenyl)-1-etanon, og-59 ml (0,6 mol) etylacetat. Oljen som oppnås etter behandlin-gen destilleres under vakuum. Oppnådd vekt; 53,7 g (Rdt: 56 %) . PE~ u 110-140°C. IR: v c = 0 = 1620 cm"<1>. RMN 0,3 mmHg (CDC14), 3 H ved 2,12 (singlett), 3 H ved 3,4 (singlett), 3 H ved 3,73 (singlett), 2 H ved 4,47 (singlett), 1 H ved 6,3 (singlett) , 3 H fra 7,0 til 7,6 (multiplett), 1 H ved 16 (utbyttbar med D20). (Enolisk form av Ø-diketon). Prepared according to Example 24 from 0.8 mol of sodium hydride, 77.77 g (0.4 mol) of (methoxymethyl-3-phenyl)-1-ethanone, and -59 ml (0.6 mol) of ethyl acetate. The oil obtained after the treatment is distilled under vacuum. Gained weight; 53.7 g (Rdt: 56%) . PE~ u 110-140°C. IR: v c = 0 = 1620 cm"<1>. RMN 0.3 mmHg (CDC14), 3 H at 2.12 (singlet), 3 H at 3.4 (singlet), 3 H at 3.73 (singlet ), 2 H at 4.47 (singlet), 1 H at 6.3 (singlet), 3 H from 7.0 to 7.6 (multiplet), 1 H at 16 (exchangeable with D20). (Enolic form of Ø-diketone).

Eksempel 3 9 Example 3 9

Brom- metyl- 8- metyl- 2- 4H-[ 1]- benzopyranon- 4 Bromo- methyl- 8- methyl- 2- 4H-[ 1]- benzopyranone- 4

C^H BrOj. PM = 253,10. C^H BrO 2 . PM = 253.10.

Fremstilt i henhold til eksempel 4 ut fra 27,4 g (0,116 mol) av (metoksy-2-metoksymetyl-3-fenyl)-1-butandion-1,3. Oppnådd vekt: 18 g. (Rdt: 61 %). PF = 126-128°C (cykloheksan/ etylacetat), IR: v c = 0 = 1670 cm . RMN (CDC13), 3 H ved 2,45 (singlett), 2 H ved 4,73 (singlett), 1 H ved- 6,27 (singlett), 1 H fra 7,1 til 7,5 (multiplett), 1 H ved 7,77 (dublett av dublett, J 1 = 8 Hz, J, ^ = 2 Hz), 1 H ved 8,2 (dublett av dublett, J1 = 8 Hz, J2 = 2 Hz). Prepared according to Example 4 from 27.4 g (0.116 mol) of (methoxy-2-methoxymethyl-3-phenyl)-1-butanedione-1,3. Achieved weight: 18 g. (Rdt: 61 %). PF = 126-128°C (cyclohexane/ethyl acetate), IR: v c = 0 = 1670 cm . NMR (CDC13), 3 H at 2.45 (singlet), 2 H at 4.73 (singlet), 1 H at 6.27 (singlet), 1 H from 7.1 to 7.5 (multiplet), 1 H at 7.77 (doublet of doublet, J 1 = 8 Hz, J, ^ = 2 Hz), 1 H at 8.2 (doublet of doublet, J1 = 8 Hz, J2 = 2 Hz).

Eksempel 4 0 Example 4 0

( Hydroksy- 2- metoksyrne tyl- 3- fenyl)- 1- feny1- 4- butandion- l, 3 C18H18°4- PM = 298 '34' ( Hydroxy- 2- methoxyrne tyl- 3- phenyl)- 1- pheny1- 4- butanedione- 1, 3 C18H18°4- PM = 298 '34'

Fremstilt i h.enhold til eksempel 3 ut fra 37 g (0,2 mol) av (hydroksy-2-metoksymetyl-3-fenyl)-1-etanon og 49,2 g (0,3 Prepared according to example 3 from 37 g (0.2 mol) of (hydroxy-2-methoxymethyl-3-phenyl)-1-ethanone and 49.2 g (0.3

mol) etylfenylacetat ved å erstatte 3N saltsyre med 50 % eddik- mol) ethyl phenyl acetate by replacing 3N hydrochloric acid with 50% acetic

syre. Etter fordampning'av* losningsmidlet oppnår man 68 g av en olje som anvendes uten sluttrensning i det følgende trinn. acid. After evaporation of the solvent, 68 g of an oil is obtained which is used without final purification in the following step.

Eksempel ' 41 Example ' 41

• Brom- metyl- 8-( fenylmetyl)- 2- 4H-[ 1]- benzopyranon- 4 <C>17<H>13Br02' PM = 329'20- • Bromo-methyl- 8-(phenylmethyl)- 2- 4H-[ 1]- benzopyranone- 4<C>17<H>13Br02' PM = 329'20-

Fremstilt i henhold til eksempel 4 ut fra (hydroksy-2-metoksymetyl-3-fenyl)-1-fenyl-4-butandion-1,3 fremstilt i det foregående eksempel. Oppnådd vekt: 47,5 g (Rdt: 72 %). PFV = 128 C (toluen/heksan). IR: v c = 0 (pyron) = 1670 cm" . RMN (CDC13) , 2 H ved 4,0 (singlett),. 2 H ved 4,63 (singlett), 1 H ved 6,23 (singlett), 6 H fra 7,1 til 7,55 (multiplett), 1 H ved 7,7 (dublett av dublett, Jx = 8 Hz, J2 = 2 Hz), 1 H ved 8,2 (dublett av dublett, ^ = 8 Hz, J2 = 2 Hz). Prepared according to example 4 from (hydroxy-2-methoxymethyl-3-phenyl)-1-phenyl-4-butanedione-1,3 prepared in the previous example. Achieved weight: 47.5 g (Rdt: 72%). PFV = 128 C (toluene/hexane). IR: v c = 0 (pyrone) = 1670 cm" . RMN (CDCl 3 ), 2 H at 4.0 (singlet), 2 H at 4.63 (singlet), 1 H at 6.23 (singlet), 6 H from 7.1 to 7.55 (multiplet), 1 H at 7.7 (doublet of doublet, Jx = 8 Hz, J2 = 2 Hz), 1 H at 8.2 (doublet of doublet, ^ = 8 Hz , J2 = 2 Hz).

Eksempel 4 2 Example 4 2

( Hydroksy- 2- metoksymetyl- 3- fenyl)- 1- fenyl- 5- penten- 4- dion- 1, 3 C19H18°4 * PM = 310'35- ( Hydroxy- 2- methoxymethyl- 3- phenyl)- 1- phenyl- 5- pentene- 4-dione- 1, 3 C19H18°4 * PM = 310'35-

Fremstilt i henhold til eksempel 24 ut fra 60 g (0,333 mol) av (hydroksy-2-metoksymetyl-3-fenyl)-1-etanon og 88 g (0,499 mol) etyl-fenyl-3-propionat. PF = 92°C (heksan/eter). Prepared according to Example 24 from 60 g (0.333 mol) of (hydroxy-2-methoxymethyl-3-phenyl)-1-ethanone and 88 g (0.499 mol) ethyl-phenyl-3-propionate. PF = 92°C (hexane/ether).

-1 -1

IR: v c = 0 = 1640 cm . RMN (CDCl3), 3 H ved 3,46 (singlett), 2 H ved 4,6 (singlett), 1 H ved 6,33 (singlett), 10 H fra 6,4 IR: v c = 0 = 1640 cm . NMR (CDCl3), 3 H at 3.46 (singlet), 2 H at 4.6 (singlet), 1 H at 6.33 (singlet), 10 H from 6.4

til 7,9 (multiplett), 1 H ved 12,6 (utbyttbar med D20), 1 H ved 14,7 (utbyttbar rned D.,0) . (Enolisk form av Ø-diketon). to 7.9 (multiplet), 1 H at 12.6 (exchangeable with D2O), 1 H at 14.7 (exchangeable rned D.,0) . (Enolic form of Ø-diketone).

Eksempel 4 3 Example 4 3

Brom- metyl- 8 - ( f enyl- 2- etenyl).- 2- 4H- [ 1 ] - benzopyranon- 4 C18H13Br0" PM = 341 '21 Bromo- methyl- 8 - ( f enyl- 2- ethenyl).- 2- 4H- [ 1 ] - benzopyranone- 4 C18H13Br0" PM = 341 '21

Fremstilt i henhold til eksempel 4 ut fra 10,2 g (0,033 mol) av (hydroksy-2-metoksymetyl-3-fenyl)-1-fenyl-5-penten-4-dion-1,3. Oppnådd vekt: 8,4 g (Rdt: 75 %). PF = 2'12°C (tolu--1 -1 en). IR: v c =0 (pyron) = 1660 cm , v c = 0 = 1640 cm . RMN (CDC13), 2 H ved 4,83 (singlett), 1 H ved 6,4 (singlett), 1 H ved 6,8 (dublett, J = 16 Hz), 8 H fra 7,1 til 7,9 (multiplett), ,1 H ved 8,2 (dublett av dublett, = 8 Hz, J2 = 2 Hz). Prepared according to Example 4 from 10.2 g (0.033 mol) of (hydroxy-2-methoxymethyl-3-phenyl)-1-phenyl-5-pentene-4-dione-1,3. Achieved weight: 8.4 g (Rdt: 75%). PF = 2'12°C (toluene--1 -1 en). IR: v c =0 (pyron) = 1660 cm , v c = 0 = 1640 cm . NMR (CDC13), 2 H at 4.83 (singlet), 1 H at 6.4 (singlet), 1 H at 6.8 (doublet, J = 16 Hz), 8 H from 7.1 to 7.9 (multiplet), .1 H at 8.2 (doublet of doublet, = 8 Hz, J2 = 2 Hz).

Claims (1)

Mellomprodukter for fremstilling av derivater av [okso-4-4H-(1)-benzopyran-8-yl]eddiksyre med formel I:Intermediates for the preparation of derivatives of [oxo-4-4H-(1)-benzopyran-8-yl]acetic acid with formula I: hvor AR representerer et fenylradikal som er substituert eller ikke en eller to ganger med et lavere alkylradikal eller et lavere alkoksyradikal, representerer et hydrogenatom eller et fenylradikal, R2 representerer et hydrogenatom eller et alkalimetall, et oksetylert alkylradikal, hydroksyetyl-, dietylaminoetyl-, dimetylaminopropyl-, morfolinoetyl-radikal,where AR represents a phenyl radical substituted or unsubstituted once or twice with a lower alkyl radical or a lower alkoxy radical, represents a hydrogen atom or a phenyl radical, R 2 represents a hydrogen atom or an alkali metal, an oxytylated alkyl radical, hydroxyethyl-, diethylaminoethyl-, dimethylaminopropyl- , morpholinoethyl radical, og X representerer et hydrogenatom eller et lavere alkoksyradikal, karakterisert ved at de er 8-bromalkyl-4H-(l)-benzopyran-4-oner med den generelle formel II:and X represents a hydrogen atom or a lower alkoxy radical, characterized in that they are 8-bromoalkyl-4H-(1)-benzopyran-4-ones of the general formula II: hvor AR, R^ og X er som definert ovenfor.where AR, R^ and X are as defined above.
NO823939A 1981-11-25 1982-11-24 INTERMEDIATES FOR THE PREPARATION OF DERIVATIVES OF (OKSO-4-4H- (1) -BENZOPYRANE-8-YL) -ACDIC ACID. NO162463C (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR8122019A FR2516921A1 (en) 1981-11-25 1981-11-25 HALOALKYL-8-4H- (1) BENZOPYRAN-4-ONES, AND METHODS OF PREPARATION

Publications (3)

Publication Number Publication Date
NO823939L NO823939L (en) 1983-05-26
NO162463B true NO162463B (en) 1989-09-25
NO162463C NO162463C (en) 1990-01-10

Family

ID=9264330

Family Applications (1)

Application Number Title Priority Date Filing Date
NO823939A NO162463C (en) 1981-11-25 1982-11-24 INTERMEDIATES FOR THE PREPARATION OF DERIVATIVES OF (OKSO-4-4H- (1) -BENZOPYRANE-8-YL) -ACDIC ACID.

Country Status (24)

Country Link
EP (1) EP0080419B1 (en)
JP (1) JPS5896038A (en)
AR (1) AR243249A1 (en)
AT (1) ATE49760T1 (en)
AU (1) AU563066B2 (en)
CA (1) CA1197511A (en)
CS (1) CS236696B2 (en)
DD (1) DD204920A5 (en)
DE (1) DE3280092D1 (en)
DK (1) DK166778B1 (en)
ES (1) ES8308322A1 (en)
FR (1) FR2516921A1 (en)
HU (1) HU194549B (en)
IE (1) IE56916B1 (en)
IL (1) IL67290A0 (en)
IN (1) IN158942B (en)
MA (1) MA19649A1 (en)
NO (1) NO162463C (en)
NZ (1) NZ202595A (en)
OA (1) OA07256A (en)
PT (2) PT75885A (en)
SU (2) SU1189344A3 (en)
YU (1) YU43808B (en)
ZA (1) ZA828435B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5002603A (en) * 1989-12-04 1991-03-26 Board Of Trustees Operating Michigan State University Method and compositions for stimulating vesicular-arbuscular mycorrhizal fungi
WO1998027080A1 (en) * 1996-12-19 1998-06-25 Agrevo Uk Limited Chromones useful as fungicides

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1270567B (en) * 1961-05-19 1968-06-20 Klinge Co Chem Pharm Fab Process for the production of basic substituted flavones
HU168753B (en) * 1974-05-03 1976-07-28
FR2326919A2 (en) * 1975-10-10 1977-05-06 Lipha Anti-inflammatory alpha-methyl-chromone-6-acetic acid derivs - produced by methylation of alpha-unsubstd. cpds. (BE190576)
FR2291745A1 (en) * 1974-11-20 1976-06-18 Lipha Anti-inflammatory alpha-methyl-chromone-6-acetic acid derivs - produced by methylation of alpha-unsubstd. cpds. (BE190576)
US3966770A (en) * 1975-03-25 1976-06-29 Smithkline Corporation 4-Hydroxy-α-[(3,4-methylenedioxyphenyl)isopropylaminoethyl]-3-(methylsulfonylmethyl)benzyl alcohol
FR2392018A1 (en) * 1977-05-27 1978-12-22 Seuref Ag 2,3-DIPHENYL-CHROMONE DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR THERAPEUTIC APPLICATION
FR2517142A1 (en) * 1981-11-20 1983-05-27 Efcis NON-VOLATILE STORAGE BISTABLE ROCKER WITH STATIC REPOSITIONING

Also Published As

Publication number Publication date
FR2516921B1 (en) 1984-02-10
IN158942B (en) 1987-02-21
EP0080419A3 (en) 1983-10-12
SU1189344A3 (en) 1985-10-30
DE3280092D1 (en) 1990-03-01
IL67290A0 (en) 1983-03-31
HU194549B (en) 1988-02-29
EP0080419B1 (en) 1990-01-24
NO162463C (en) 1990-01-10
AU563066B2 (en) 1987-06-25
JPH0411545B2 (en) 1992-02-28
ES517636A0 (en) 1983-08-16
ZA828435B (en) 1983-09-28
DK522982A (en) 1983-05-26
EP0080419A2 (en) 1983-06-01
ES8308322A1 (en) 1983-08-16
IE56916B1 (en) 1992-01-29
CS236696B2 (en) 1985-05-15
NZ202595A (en) 1986-02-21
IE822753L (en) 1983-05-25
AR243249A1 (en) 1993-07-30
DD204920A5 (en) 1983-12-14
DK166778B1 (en) 1993-07-12
SU1232146A3 (en) 1986-05-15
PT75885A (en) 1982-12-01
YU43808B (en) 1989-12-31
ATE49760T1 (en) 1990-02-15
PT75886A (en) 1982-12-01
NO823939L (en) 1983-05-26
AU9072882A (en) 1983-06-02
JPS5896038A (en) 1983-06-07
FR2516921A1 (en) 1983-05-27
OA07256A (en) 1984-04-30
MA19649A1 (en) 1983-07-01
YU264882A (en) 1984-12-31
CA1197511A (en) 1985-12-03

Similar Documents

Publication Publication Date Title
US3484445A (en) Derivatives of chromone-2-carboxylic acid
NO800796L (en) PROCEDURE FOR THE PREPARATION OF THERAPEUTICALLY EFFECTIVE CHROMONDERIVATIVES
US4337263A (en) 1-Aryl-4-γ-arylsulphonyl-3-aminopropoxy-1H-pyrazoles and their use as hypolipemiant and hypocholesterolemiant agents
NO167693B (en) SYSTEM FOR CYCLIC INTERRUPTION OF OPERATION OF A DEVICE BETWEEN A FIRST AND A second condition.
JPS6339587B2 (en)
EP0669924B1 (en) Regioselective synthesis of 4-chloro-2-thiophenecarboxylic acid
SU638259A3 (en) Method of obtaining 2,3-substituted 5,6-condensed 4-(2h)-aminoalkoxypyranones or salts thereof
NO162463B (en) INTERMEDIATES FOR THE PREPARATION OF DERIVATIVES OF (OKSO-4-4H- (1) -BENZOPYRANE-8-YL) -ACDIC ACID.
NO742077L (en)
NO327039B1 (en) 3- (1-Hydroxy-pentylidene) -5-nitro-3H-benzofuran-2-one, Process for Preparation and Use thereof
EP1064265B8 (en) Synthesis of 3-amino-2-chloro-4-methylpyridine from malononitrile and acetone
JP3647455B2 (en) Method for producing 3-isoxazolecarboxylic acid
JP2612161B2 (en) Method for producing dibenzothiepine derivatives
Sato et al. Studies on pyrazines. 35. An improved synthesis of bromopyrazines from hydroxypyrazines
NO155666B (en) PROCEDURE FOR THE PREPARATION OF 5,6,7,7A-TETRAHYDRO-4H-THIENO- (3,2-C) -PYRIDIN-2-ON DERIVATIVES.
JP2549997B2 (en) New haloketal compound
EP0725785B1 (en) Process for the preparation of rufloxacin and salts thereof
US4891433A (en) Process for the preparation of dibenzothiepin derivative
NO122754B (en)
Dimsdale The formation of 2‐alkoxyquinolines from quinoline N‐oxides in alcoholic media
NO750877L (en)
JPS61246176A (en) Preparation of aminolactone
NO751362L (en)
KR920005417B1 (en) Process for preparing of dibezothiepin derivative
NO152006B (en) PROCEDURE FOR PREPARING 4-SUBSTITUTED 1,2-DIPHENYL-3,5-DIOXOPYRAZOLIDINES