CA2438878A1 - Continuous process for preparing dihydropyrones - Google Patents
Continuous process for preparing dihydropyrones Download PDFInfo
- Publication number
- CA2438878A1 CA2438878A1 CA002438878A CA2438878A CA2438878A1 CA 2438878 A1 CA2438878 A1 CA 2438878A1 CA 002438878 A CA002438878 A CA 002438878A CA 2438878 A CA2438878 A CA 2438878A CA 2438878 A1 CA2438878 A1 CA 2438878A1
- Authority
- CA
- Canada
- Prior art keywords
- process according
- formula
- compound
- acetoacetate
- reaction
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a continuous method for producing dihydropyrones of general formula (I), whereby radicals R1 and R2 can have the meanings as cit ed in the claims.
Claims (12)
1. Process for preparing a compound of general formula (I), wherein R1 denotes a C1-C6-alkyl, C6-C10-aryl-C1-C4-alkyl or C3-C8-cycloalkyl-C1-C4-alkyl group, and R2 denotes a C1-C8-alkyl group, by reacting a) a ketone of formula (II) wherein R1 and R2 are as hereinbefore defined, with an acetoacetate in the presence of a strong base and b) by cyclising the resulting compound of formula (IV) wherein R3 denotes a C1-C4-alkyl or benzyl group, by means of a base, characterised in that a compound of formula II is continuously mixed and reacted with an acetoacetate in the form of its dianion in a microreactor.
2. Process according to claim 1, characterised in that a microreactor with an interdigital channel structure is used for reaction step a).
3. Process according to claim 1 or 2, characterised in that a current of educt A
containing the compound of formula (II) and a current of educt B containing the acetoacetate in the form of its dianion are continuously mixed together in the mixing element of a microreactor and the liquid reaction mixture is passed into a holding capillary.
containing the compound of formula (II) and a current of educt B containing the acetoacetate in the form of its dianion are continuously mixed together in the mixing element of a microreactor and the liquid reaction mixture is passed into a holding capillary.
4. Process according to one of claims 1 - 3 , characterised in that the capillary is 0.1 to 10 m long and 0.05 to 5 mm in diameter.
5. Process according to one of claims 1 - 4, characterised in that 1-phenyl-3-hexanone is used as the compound of formula (II) in step a).
6. Process according to one of claims 1 - 5, characterised in that in step a) the acetoacetate is used in the presence of at least 2 equivalents of a strong base selected from among sodium hydride, butyllithium and lithium dialkylamide.
7. Process according to one of claims 1 - 6, characterised in that the acetoacetate is added to the compound of formula (II) in a molar ratio of 2:1 to 1:2.
8. Process according to one of claims 1 - 7, characterised in that the reaction in step a) is carried out at a temperature of -78 to +85 °C.
9. Process according to one of claims 1 - 9, characterised in that the reaction in step a) is carried out at an overall flow rate of 1.5 to 5 ml/min.
10. Process according to one of claims 1 - 9, characterised in that the flow rate of the compound of formula (II) to the compound of formula (III) is in a ratio of 1:1 to 1:2.
11.Process according to one of claims 1 - 10, characterised in that the reaction is carried out in a plurality of microreactors connected in series or in parallel.
12. Use of the 5,6-dihydro-4-hydroxy-6-phenethyl-6-propyl-2H-pyran-2-one obtained by a process according to one of claims 1 - 11 for the preparation of tipranavir.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10108471.4 | 2001-02-22 | ||
| DE2001108471 DE10108471C1 (en) | 2001-02-22 | 2001-02-22 | Continuous process for the preparation of 5,6-dihydro-4-hydroxy-2-pyrones |
| PCT/EP2002/001772 WO2002068403A1 (en) | 2001-02-22 | 2002-02-20 | Continuous method for producing dihydropyrones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2438878A1 true CA2438878A1 (en) | 2002-09-06 |
| CA2438878C CA2438878C (en) | 2010-05-04 |
Family
ID=7675073
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2438878A Expired - Fee Related CA2438878C (en) | 2001-02-22 | 2002-02-20 | Continuous process for preparing dihydropyrones |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1368331B1 (en) |
| JP (1) | JP4335529B2 (en) |
| CA (1) | CA2438878C (en) |
| DE (1) | DE10108471C1 (en) |
| MX (1) | MXPA03007531A (en) |
| WO (1) | WO2002068403A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10257761A1 (en) * | 2002-12-10 | 2004-06-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Preparation of optically active 5-hydroxy-3-ketoalkanoic acid ester derivatives used as intermediates for drugs, especially tipranavir, by optical resolution of racemate by preparative high performance liquid chromatography |
| DE10303581A1 (en) * | 2003-01-30 | 2004-08-12 | Clariant Gmbh | Acetoacetylation of alcohols, thiols and amines in the microreactor |
| DE10333174A1 (en) * | 2003-07-22 | 2005-02-17 | Cpc Cellular Process Chemistry Systems Gmbh | Method of performing an in situ quenching reaction |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE263761T1 (en) | 1993-11-19 | 2004-04-15 | Parke Davis & Co | 5,6-DIHYDROPYRON DERIVATIVES AS PROTEASE INHIBITORS AND ANTIVIRAL AGENTS |
| US5834506A (en) | 1996-11-01 | 1998-11-10 | Warner-Lambert Company | Dihydropyrones with improved antiviral activity |
| DE19708472C2 (en) | 1997-02-20 | 1999-02-18 | Atotech Deutschland Gmbh | Manufacturing process for chemical microreactors |
| US6380400B1 (en) | 1998-09-11 | 2002-04-30 | Victor Fedij | Methods of making dihydropyrone HIV protease inhibitors |
| DE19935691A1 (en) | 1999-07-29 | 2001-02-01 | Merck Patent Gmbh | Friedel-Crafts acylation in a static micromixer |
| DE10001317A1 (en) | 2000-01-14 | 2001-07-19 | Merck Patent Gmbh | Reaction of carbonyl compound with organometallic reagent, e.g. preparation of biotin intermediate or 4-(4-(trans-4-pentylcyclohexyl) -1-cyclohexen-1-yl)-1-trifluoromethoxybenzene, uses mini- or microreactor |
-
2001
- 2001-02-22 DE DE2001108471 patent/DE10108471C1/en not_active Expired - Fee Related
-
2002
- 2002-02-20 JP JP2002567917A patent/JP4335529B2/en not_active Expired - Fee Related
- 2002-02-20 WO PCT/EP2002/001772 patent/WO2002068403A1/en active Application Filing
- 2002-02-20 CA CA2438878A patent/CA2438878C/en not_active Expired - Fee Related
- 2002-02-20 EP EP02719875.3A patent/EP1368331B1/en not_active Expired - Lifetime
- 2002-02-20 MX MXPA03007531A patent/MXPA03007531A/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004522784A (en) | 2004-07-29 |
| MXPA03007531A (en) | 2003-12-04 |
| JP4335529B2 (en) | 2009-09-30 |
| WO2002068403A1 (en) | 2002-09-06 |
| DE10108471C1 (en) | 2002-11-21 |
| CA2438878C (en) | 2010-05-04 |
| EP1368331B1 (en) | 2014-04-09 |
| EP1368331A1 (en) | 2003-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2437702A1 (en) | Method of synthesizing camptothecin-relating compounds | |
| Eisch et al. | Stereospecific preparation of 1, 2-epoxyalkyllithium reagents via the generalized lithiation of a-heterosubstituted epoxides1 | |
| CN109232363B (en) | Synthetic method of 3-selenocyanoindole compound | |
| PL366372A1 (en) | Process and intermediates to prepare latanoprost | |
| CA2438878A1 (en) | Continuous process for preparing dihydropyrones | |
| WO2005003374A3 (en) | SYNTHESIS OF β-L-2-DEOXY NUCLEOSIDES | |
| JPWO2006077854A1 (en) | Method for producing imide ether compound | |
| Tanaka et al. | A simple, stereocontrolled synthesis of α-alkylidene-γ-butyrolactones | |
| JP2004522784A5 (en) | ||
| EA200500896A1 (en) | METHOD OF OBTAINING OLEFINS | |
| CN114213312A (en) | Synthesis method of visible light promoted 3-selenocyanoindole compound | |
| CN108084157A (en) | A kind of synthetic method of Ni Lapani | |
| EP1151987A1 (en) | Optically active fluorinated binaphthol derivative | |
| Koketsu et al. | Syntheses of cyanoselenoamides and diselenoamides: Conversion into selenazoles and selenazines | |
| KR20110090821A (en) | A new method of preparing a secondary amine compound using a microflow reactor | |
| CN106117147B (en) | Miscellaneous tall and erect class compound of naphtho- and the preparation method and application thereof | |
| CN104774183A (en) | Preparation method of formoxyl rosuvastatin calcium intermediate | |
| CN105017077B (en) | A kind of synthetic method of imidoether derivative | |
| JP2010030940A (en) | Method for synthesizing 4-methoxysalicylic acid | |
| DE50203881D1 (en) | MARKABLE COMPOUNDS FOR THE SIMPLE SYNTHESIS OF 3 '- [18F] FLUORO-3'-DEOXYTHYMIDINE AND PROCESS FOR THE PRODUCTION THEREOF | |
| CN114805127B (en) | Preparation method of 2-trifluoromethyl-1-tetralone compound | |
| CN108409672A (en) | A kind of method that mantoquita catalyzes and synthesizes polysubstituted pyrimidine | |
| CN110683943B (en) | Fluoro 1, 3-eneyne compound and preparation method thereof | |
| CN101555225B (en) | Method for preparing poly-substituted quinoline compound | |
| KR100515591B1 (en) | METHOD FOR PREPARING OF 4[(N-(tert-butoxycarbonyl)amino)methylene]-1-N-(tert-butoxycarbonyl)pyrrolidine-3-one |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20160222 |