NL8700358A - CHEMICAL METHOD. - Google Patents
CHEMICAL METHOD. Download PDFInfo
- Publication number
- NL8700358A NL8700358A NL8700358A NL8700358A NL8700358A NL 8700358 A NL8700358 A NL 8700358A NL 8700358 A NL8700358 A NL 8700358A NL 8700358 A NL8700358 A NL 8700358A NL 8700358 A NL8700358 A NL 8700358A
- Authority
- NL
- Netherlands
- Prior art keywords
- formula
- compound
- process according
- hal
- carried out
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 18
- 239000000126 substance Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 150000007857 hydrazones Chemical class 0.000 description 3
- 229960004270 nabumetone Drugs 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- JYLGKVDVIPITQM-UHFFFAOYSA-N 2-(chloromethyl)-6-methoxynaphthalene Chemical compound C1=C(CCl)C=CC2=CC(OC)=CC=C21 JYLGKVDVIPITQM-UHFFFAOYSA-N 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/72—Hydrazones
-
- 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
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/516—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of nitrogen-containing compounds to >C = O groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
- Chemische werkwijze -- Chemical method -
De uitvinding heeft betrekking op een werkwijze voor de bereiding van 4-(6-methoxy-2-na£tyl)butan-2-on en op tussenprodukten die bij deze synthese gebruikt kunnen worden.The invention relates to a process for the preparation of 4- (6-methoxy-2-sodium) butan-2-one and to intermediates which can be used in this synthesis.
^ Het Amerikaanse octrooischrift 4.061.779 beschrijft 4-(6-methoxy-2-naftyl)-butan-2-on (nabumeton) en het gebruik ervan bij de behandeling van rheumatische en artritische aandoeningen. Een aantal werkwijzen voor de bereiding van de verbinding worden eveneens beschreven. De Amerikaanse octrooi- ^ schriften 4.221.741 en 4.247.709 beschrijven andere werkwijzen voor de bereiding van nabumeton.^ U.S. Patent 4,061,779 describes 4- (6-methoxy-2-naphthyl) -butan-2-one (nabumetone) and its use in the treatment of rheumatic and arthritic conditions. A number of methods for the preparation of the compound are also described. U.S. Patents 4,221,741 and 4,247,709 describe other processes for the preparation of nabumetone.
Een nieuwe werkwijze voor de bereiding van nabumeton is nu gevonden , welke werkwijze gekenmerkt wordt door de vorming van een hydrazon, gevolgd door hydrolyse.A new process for the preparation of nabumetone has now been found, which process is characterized by the formation of a hydrazone followed by hydrolysis.
^ Dienovereenkomstig verschaft de uitvinding een werkwijze voor de bereiding van 4-(6-methoxy-2-naftyl)butan-2-on^ welke werkwijze omvat de reaktie van een verbinding met formule 1 waarin Hal halogeen is , met een verbinding piet formule 2 waarin M een alkalimetaal is en R. en R alkylgroepen 20 · ^ met 1 tot 6 koolstofatomen zijn, gevolgd door zure hydrolyse.Accordingly, the invention provides a process for the preparation of 4- (6-methoxy-2-naphthyl) butan-2-one, which process comprises reacting a compound of formula 1 wherein Hal is halogen, with a compound of formula 2 wherein M is an alkali metal and R 1 and R are alkyl groups of 1 to 6 carbon atoms, followed by acid hydrolysis.
Hal is bij voorkeur chloor en MHal is preferably chlorine and M.
is bij voorkeur lithium. Rj en R2 zijn bij voorkeur beide methyl.is preferably lithium. Preferably R 1 and R 2 are both methyl.
De reaktie heeft in een inert oplosmiddel , zoals tetrahydrofuran, bij omgevingstemperatuur plaats.The reaction takes place in an inert solvent, such as tetrahydrofuran, at ambient temperature.
^ De reaktie geschiedt via een tussenprodukt met formule 3. De erop volgende hydrolyse van de verbinding met formule 3 heeft plaats onder zure omstandigheden met bijvoorbeeld zoutzuur/water bij omgevingstemperatuur, bijvoorbeeld 20-30°C.The reaction takes place via an intermediate of the formula 3. The subsequent hydrolysis of the compound of the formula 3 takes place under acidic conditions with, for example, hydrochloric acid / water at ambient temperature, for example 20-30 ° C.
ΟΛ ^ #ΟΛ ^ #
De verbinding met formule 2 wordt doelmatig in situ bereid uit aceton en Ν,Ν-dimethylhydrazine.The compound of formula II is conveniently prepared in situ from acetone and Ν, Ν-dimethylhydrazine.
Verbindingen met de formule 1 zijn bekend.Compounds of the formula I are known.
Verbindingen met formule 3 zijn nieuw en vormen een aspect van de uitvinding .Compounds of formula 3 are new and form an aspect of the invention.
OC ...OC ...
Het volgende voorbeeld licht de uitvinding toe.The following example illustrates the invention.
8700358 *·» Ni 9 - 2 -8700358 * · »Ni 9 - 2 -
Voorbeeld (zie reaktieschema A)Example (see reaction scheme A)
Het hydrazon met formule 4 werd kwantitatief verkregen als een olie uit 2-chloormethyl-6-methoxynaftaleen en het in situ bereide lithium-N,N'-dimethylhydrazon van aceton 5 (zie Yamashita et. al. Bull.Chem. Soc. Jpn 58 , 407-408 (1985)).The hydrazone of formula 4 was obtained quantitatively as an oil from 2-chloromethyl-6-methoxynaphthalene and the lithium N, N'-dimethylhydrazone of acetone 5 prepared in situ (see Yamashita et. Al. Bull. Chem. Soc. Jpn 58 407-408 (1985)).
Het hydrazon met formule 4 werd behandeld met 5 M zoutzuur' bij kamertemperatuur onder verkrijging van het produkt met formule 5 in 95% opbrengst en met een zuiverheid van 80% (opbrengst aan zuiver produkt 76%).The hydrazone of the formula IV was treated with 5 M hydrochloric acid at room temperature to obtain the product of the formula 5 in 95% yield and with a purity of 80% (yield of pure product 76%).
10 870035810 8700358
Claims (10)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8603778 | 1986-02-15 | ||
| GB868603778A GB8603778D0 (en) | 1986-02-15 | 1986-02-15 | Chemical process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8700358A true NL8700358A (en) | 1987-09-01 |
Family
ID=10593134
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8700358A NL8700358A (en) | 1986-02-15 | 1987-02-13 | CHEMICAL METHOD. |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS62195344A (en) |
| CH (1) | CH670084A5 (en) |
| DK (1) | DK75487A (en) |
| ES (1) | ES2004879A6 (en) |
| GB (1) | GB8603778D0 (en) |
| GR (1) | GR870258B (en) |
| NL (1) | NL8700358A (en) |
| SE (1) | SE465926B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5756851A (en) * | 1996-10-21 | 1998-05-26 | Albemarle Corporation | Production of nabumetone or precursors thereof |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4943579A (en) * | 1987-10-06 | 1990-07-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Water soluble prodrugs of camptothecin |
| DE3829586A1 (en) * | 1988-09-01 | 1990-03-22 | Bayer Ag | DISUBSTITUTED NAPHTHALINE, METHOD FOR THE PRODUCTION AND THEIR USE OF HERBICIDES |
| CU23844B1 (en) * | 2009-04-17 | 2012-10-15 | Ct De Neurociencias De Cuba | PROCEDURE FOR OBTAINING NEW DERIVATIVES OF NAFTALENE FOR THE LIVE DIAGNOSIS OF ALZHEIMER'S DISEASE |
-
1986
- 1986-02-15 GB GB868603778A patent/GB8603778D0/en active Pending
-
1987
- 1987-02-13 NL NL8700358A patent/NL8700358A/en not_active Application Discontinuation
- 1987-02-13 DK DK75487A patent/DK75487A/en unknown
- 1987-02-13 CH CH53687A patent/CH670084A5/en not_active IP Right Cessation
- 1987-02-13 GR GR870258A patent/GR870258B/en unknown
- 1987-02-13 SE SE8700594A patent/SE465926B/en unknown
- 1987-02-13 ES ES8700375A patent/ES2004879A6/en not_active Expired
- 1987-02-14 JP JP3229587A patent/JPS62195344A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| M. YAMASHITA ET AL.: "The Facile Synthesis of Unsymmetrical Ketones Using Acetone Dimethylhydrazone", BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, vol. 58, 1985, TOKYO JP, pages 407 - 408 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5756851A (en) * | 1996-10-21 | 1998-05-26 | Albemarle Corporation | Production of nabumetone or precursors thereof |
| US5907069A (en) * | 1996-10-21 | 1999-05-25 | Albemarle Corporation | Production of nabumetone or precursors thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| SE8700594D0 (en) | 1987-02-13 |
| JPS62195344A (en) | 1987-08-28 |
| GR870258B (en) | 1987-06-16 |
| ES2004879A6 (en) | 1989-02-16 |
| SE8700594L (en) | 1987-08-16 |
| SE465926B (en) | 1991-11-18 |
| DK75487A (en) | 1987-08-16 |
| GB8603778D0 (en) | 1986-03-19 |
| DK75487D0 (en) | 1987-02-13 |
| CH670084A5 (en) | 1989-05-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BA | A request for search or an international-type search has been filed | ||
| BB | A search report has been drawn up | ||
| BV | The patent application has lapsed |