WO1996008502A1 - Preparation of (8s)-8-fluoroerythromycins with n-f fluorinating agents - Google Patents
Preparation of (8s)-8-fluoroerythromycins with n-f fluorinating agents Download PDFInfo
- Publication number
- WO1996008502A1 WO1996008502A1 PCT/US1995/011098 US9511098W WO9608502A1 WO 1996008502 A1 WO1996008502 A1 WO 1996008502A1 US 9511098 W US9511098 W US 9511098W WO 9608502 A1 WO9608502 A1 WO 9608502A1
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- WO
- WIPO (PCT)
- Prior art keywords
- agent
- fluoπnating
- fluoro
- acetic acid
- carboxylic acid
- Prior art date
Links
- 239000012025 fluorinating agent Substances 0.000 title abstract description 15
- 238000002360 preparation method Methods 0.000 title description 10
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 60
- 238000000034 method Methods 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 150000001735 carboxylic acids Chemical class 0.000 claims description 12
- -1 tetrafluoroborate Chemical compound 0.000 claims description 12
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical group C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 claims description 10
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical class CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 10
- 239000006184 cosolvent Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Natural products O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 abstract description 20
- XOEUHCONYHZURQ-HNUBZJOYSA-N flurithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@@](C)(F)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 XOEUHCONYHZURQ-HNUBZJOYSA-N 0.000 abstract description 14
- 238000011065 in-situ storage Methods 0.000 abstract description 3
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 abstract description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 229960000583 acetic acid Drugs 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 229960003276 erythromycin Drugs 0.000 description 13
- 229960001398 flurithromycin Drugs 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000012362 glacial acetic acid Substances 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 229930006677 Erythromycin A Natural products 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 238000003682 fluorination reaction Methods 0.000 description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- UWDCUCCPBLHLTI-UHFFFAOYSA-N 1-fluoropyridin-1-ium Chemical class F[N+]1=CC=CC=C1 UWDCUCCPBLHLTI-UHFFFAOYSA-N 0.000 description 3
- ILXAULYORNMOAX-UHFFFAOYSA-N 2-fluoro-1$l^{6},3$l^{6},2-benzodithiazole 1,1,3,3-tetraoxide Chemical compound C1=CC=C2S(=O)(=O)N(F)S(=O)(=O)C2=C1 ILXAULYORNMOAX-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- PBJTXVTVKNXWHU-UHFFFAOYSA-N dioxidoboranyloxy(fluoro)borinate 1-fluoropyridin-1-ium pyridine Chemical compound C1=CC=NC=C1.[O-]B([O-])OB([O-])F.[O-]B([O-])OB([O-])F.[O-]B([O-])OB([O-])F.[O-]B([O-])OB([O-])F.[O-]B([O-])OB([O-])F.[O-]B([O-])OB([O-])F.[O-]B([O-])OB([O-])F.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1.F[N+]1=CC=CC=C1 PBJTXVTVKNXWHU-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- XHFXMNZYIKFCPN-UHFFFAOYSA-N perchloryl fluoride Chemical compound FCl(=O)(=O)=O XHFXMNZYIKFCPN-UHFFFAOYSA-N 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000007806 chemical reaction intermediate Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- LUIPOVCSQJTWHA-RWJQBGPGSA-N (2s,3r,4s,6r)-2-[[(3r,4s,5s,6r,7r,9r,11r,12r,13s,14r)-14-ethyl-7,12,13-trihydroxy-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-6-yl]oxy]-3-hydroxy-n,n,6-trimethyloxan-4-amine oxide Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)[N+](C)(C)[O-])O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 LUIPOVCSQJTWHA-RWJQBGPGSA-N 0.000 description 1
- XYNFYYSUAXXVKW-UHFFFAOYSA-N 1-fluoro-2h-pyridin-1-ium-1-sulfonate Chemical class [O-]S(=O)(=O)[N+]1(F)CC=CC=C1 XYNFYYSUAXXVKW-UHFFFAOYSA-N 0.000 description 1
- 101100257262 Caenorhabditis elegans soc-1 gene Proteins 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- OXZOLXJZTSUDOM-UHFFFAOYSA-N fluoro 2,2,2-trifluoroacetate Chemical compound FOC(=O)C(F)(F)F OXZOLXJZTSUDOM-UHFFFAOYSA-N 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylene diamine Substances C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
Definitions
- the present invention relates to a process for the synthesis of (8S)-8- fluoroerythromycins which are well known as useful antibacterial agents and are described in U.S. Patents 4,673,736 and 4,514,562.
- the current methods for preparing (8S)-8-fluoroerythromycins involve either treatment of 8,9-anhydroerythromycin 6,9-hemiacetals or their N-oxides with fluorinating agents such as perchloryl fluoride, fluoroxyperfluoroalkanes, fluoroxysulf ⁇ rpentafluoride, molecular fluorine, lead tetracetate hydrogen fluoride or trifluoroacetylhypofluorite (U.S. Patent 4,514,562). More recently, the preparation of (8S)-8-fluoroerythromycins has been improved by exposure of erythromycin to perchloryl fluoride in an acetic acid buffer and an inert co-solvent (U.S.
- Patent 4,673,736 The aforementioned fluorinating agents have disadvantages; such as: hazards in handling, relatively high cost, the need for special reaction vessels, and chemical instability, which make them unsatisfactory for preparing commercial quantities of (8S)-8-fluoroerythromycins
- Perchloryl fluoride in particular, is known to form unstable and explosive organoperchlorates in reactions with organic molecules. See Peet, H. H. J and Rocket, B W. J. Organometal. Chem. 82, C57 ( 1974) and Adcock. W and Khor, J. C. ibid.
- N-F (electrophi c) fluorinating agents characte ⁇ zed by a structure containing an N-F bond
- reagents for introducing fluorine into organic molecules As a class, they have been shown to be stable due to their ability to be stored for long pe ⁇ ods of time and high melting points and are easilv handled reagents
- This invention relates to a process for prepa ⁇ ng (8S)-8-fluoroerythromyc ⁇ ns comp ⁇ sing reacting 8,9-anhydroerythromycin 6,9-hemiacetals or an N-oxide thereof with a carboxylic acid and an N-F fluo ⁇ nating agent for a sufficient time and temperature to obtain an (8S)-8-fluoroerythromyc ⁇ n
- An additional embodiment of the invention comp ⁇ ses prepa ⁇ ng the 8,9-anhydroerythromycin 6,9-hem ⁇ acetal starting matenal from erythromycin or an N-oxide de ⁇ vative thereof and using same in situ for the reaction to form the (8S)-8-fluoroerythromyc ⁇ n
- the reaction avoids the use of matenals which are characte ⁇ stically hazardous and/or expensive, while removing the need for a co-solvent Detailed Description of the Invention
- erythromycin or an N-oxide thereof is reacted with an N-F fluorinating agent in the presence of a carboxylic acid.
- N-F fluorinating agents are a well known class of organic compounds which are characterized by an N-F bond. These compounds can also be substituted with a variety of substituents which do not interefere with the fluorination reaction. Examples of substituents which may be present on the N-F fluorinating agents which do not interfere with the fluorination reactions include, for example, alkyl, alkoxy, Cl, Br, F, haloalkyl, phenyl, cycloalkyl and cyano.
- the N-F fluorinating agent can contain radioactive ⁇ F in lieu of ⁇ F to give radiolabelled products.
- N-fluorobenzenesulfonimide N-fluorobenzenesulfonimide and derivatives (U.S.P. 5, 1 16,982), N-fluoromethanesulfonimide and derivatives, N-fluoropyridinium pyridine heptafluorodiborate (NFPy), l-chloromethyl-4-fluoro-l,4- diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) [F-TEDA] and other 1 -alkyl-4- fluoro-l,4-diazoniabicyclo[2.2.2]octane salts and fluorinated diazabicycloalkane derivatives thereof (U.S.P.
- N-F fluo ⁇ nating agent is represented by the broad-class of N-F fluo ⁇ nating agents defined which do not contain a py ⁇ dine nucleus
- the preferred N-F fluo ⁇ nating agents are the fluo ⁇ nated diazabicycloalkane compounds desc ⁇ bed in U S P 5,086, 178, the N-fluorobenzenesulfonimides desc ⁇ bed in U S P 5,254,732, the 1- subst ⁇ tuted-4-fluoro-l,4-d ⁇ azoruab ⁇ cyclo[2 2 2]octane salts desc ⁇ bed in co-pending, commonly assigned application Se ⁇ al No 173,297, filed December 23, 1993, which application is incorporated by reference herein, and N-fluorodimethylsulfonimide and de ⁇ vatives as referred to in Journal of Fluo ⁇ ne Chemistry,
- the carboxylic acid may be any compound having a -COOH functionality, but is preferably a branched or straight chain carboxylic acid, which may be substituted with a va ⁇ ety of substituents such as halogens, electron donating or electron withdrawing groups, having a pKa which is less than or equal to that of acetic acid Still preferably, the carboxylic acid has from 2-8 carbon atoms and, most preferably, is acetic acid
- the concentration of the carboxylic acid in the reaction mixture is preferably about 0 05M to 1 5M and about 0 25M to 0 5M
- the process is conducted in the absence of an men co-solvent, such as used in the p ⁇ or art N-F fluo ⁇ nating reactions.
- the carboxylic acid is preferably buffered to a pH of about 4-7 and, more preferably, about 4-4 5 with any suitable buffering agent such as an alkali metal hydroxide, e g NaOH, KOH or LiOH Good labds of the fluoroerythromv cin products are obtained wnen 8,9- ar.hvdroervthromvci ⁇ 6.9-hem ⁇ acetals or the corresponding N-oxides are reacted with N ' -F fluo ⁇ nating agents in accordance with the invention
- the anhydro reactant is reacted with at least about one molar equivalent of an N-F fluo ⁇ nating agent for about 1 to about 30 hours, preferably, about 10 to about 24 hours
- the reaction is preferably conducted at a temperature ranging from about -5 to about 50°C at atmosphe ⁇ c pressure, still preferably, at about 10 to about
- the 8,9-anhydroeryihromyc ⁇ n 6,9- hemiacetals or the corresponding N-oxides are prepared as unisolated reaction intermediates by the action of a carboxylic acid on erythromycin or the corresponding N-oxides
- a solution of erythromycin or the corresponding N-oxides dissolved in the carboxylic acid is allowed to mix as needed to form the anhydro de ⁇ vative
- the reaction time is from about 1 minute to about 24 hours and, still preferably, from about 2 hours to about 4 hours
- the anhydro formation takes place at a reaction temperature of about -5 to about 50°C
- the reaction temperature is about 20 to about 30°C
- the anhydro unisolated intermediate may then be used in situ to prepare the fluoroervthromycin with an N-F fluo ⁇ nating agent as desc ⁇ bed above
- Erythromycin A (0.5g, 0.681 mmole) was dissolved in glacial acetic acid (4 mL) at room temperature and stirred for 2 hours The pH of the mixture was adjusted to 4 3 with 6 N sodium hydroxide (approx 1.2 mL) while the temperature was maintained below 20°C.
- N-fluoropyridinium pvridine heptafluorodiborate (0 25g, 0 75 mmole) was added and stirring continued for an additional 2 hours at 22°C.
- Example 4 The reaction was worked up in the same manner as Example 1 to afford an 11% yield of crude flurithromycin Although the yield was only 1 1%, this example demonstrates operation of the invention with N-F fluorinating agents derived from pvridine since with a co-solvent no flurithromycin is formed (See Comparative Example 4)
- Example 4 demonstrates operation of the invention with N-F fluorinating agents derived from pvridine since with a co-solvent no flurithromycin is formed (See Comparative Example 4)
- Erythromycin A (5 g, 6 813 mmole) was dissolved in glacial acetic acid (20 mL) at room temperature and stirred for 2 hours The pH of the mixture was adjusted to 4 3 with 6 N sodium hydroxide (approx 12 5 mL) while the temperature was maintained below 20 °C l -Hydroxyl-4-fluoro- l,4-d ⁇ azoruab ⁇ cyclo[2 2 2]octane b ⁇ s(tetrafluoroborate) (2 2 g, 6 813 mmole) was added and stimng continued for an additional 18 hours at 22°C Methylene chlo ⁇ de ( 100 mL) was added, the solution placed in an ice bath while the pH of the mixture was adjusted to 9 with 6 N sodium hydroxide (approx 85 mL) and the temperature maintained below 20 °C Next, water ( 100 mL) was added, the layers separated and the aqueous layer washed an additional two times with methylene
- Anhydroerythromvcin A ( 1 g. 1 4 mmole) was dissolved in glacial acetic acid (4-mL) at room temperature and the pH of the mixture was adjusted to 4 3 with 6 N sodium hydroxide (approx. 2 5 mL) while the temperature was maintained below
- the solution was diluted with methylene chloride (1 mL), washed twice with saturated NaHCO (1 mL), dried through MgSU4 and evaporated to afford only decomposition products.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU35008/95A AU3500895A (en) | 1994-09-14 | 1995-09-05 | Preparation of (8s)-8-fluoroerythromycins with n-f fluorinating agents |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/305,626 | 1994-09-14 | ||
| US08/305,626 US5552533A (en) | 1994-09-14 | 1994-09-14 | Preparation of (8S)-8-fluoroerythromycins with N-F fluorinating agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1996008502A1 true WO1996008502A1 (en) | 1996-03-21 |
Family
ID=23181608
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1995/011098 WO1996008502A1 (en) | 1994-09-14 | 1995-09-05 | Preparation of (8s)-8-fluoroerythromycins with n-f fluorinating agents |
Country Status (4)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016023178A (ja) * | 2014-07-24 | 2016-02-08 | 国立大学法人 名古屋工業大学 | フルオロマロン酸エステル誘導体の製造方法 |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4313664C2 (de) * | 1993-04-20 | 1996-12-05 | Schering Ag | N-Fluormethansulfonimid, Verfahren zu seiner Herstellung sowie dessen Verwendung |
| US7265249B2 (en) * | 2005-01-18 | 2007-09-04 | California Institute Of Technology | Enantioselective alpha-fluorination of aldehydes using chiral organic catalysts |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4514562A (en) * | 1981-11-27 | 1985-04-30 | Pierrel Spa | Fluorinated erythromycin compounds and a process for preparation |
| EP0177030A1 (en) * | 1984-10-02 | 1986-04-09 | Daikin Industries, Limited | Process for preparing 8-fluoroerythronolide |
| US4673736A (en) * | 1983-07-18 | 1987-06-16 | Pierrel Spa | Process for the preparation of (8S)-8-fluoroerythromycins |
| US5086178A (en) * | 1990-09-20 | 1992-02-04 | Air Products And Chemicals, Inc. | Fluorinated diazabicycloalkane derivatives |
| US5254732A (en) * | 1992-02-28 | 1993-10-19 | Allied-Signal Inc. | N-fluorosulfonimides and their application as fluorinating agents |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3674773A (en) * | 1970-10-06 | 1972-07-04 | Abbott Lab | Erythromycin derivatives |
| US5081249A (en) * | 1985-06-03 | 1992-01-14 | Sagami Chemical Research Center | N-fluoropyridinium-Sulfonates and a process for their preparation |
| JPH0819103B2 (ja) * | 1989-04-18 | 1996-02-28 | 財団法人相模中央化学研究所 | ２―ハロピリジン―６―スルホン酸及びその塩 |
| US4935519A (en) * | 1989-05-12 | 1990-06-19 | Allied-Signal Inc. | N-fluoropyridinium pyridine heptafluorodiborate |
| US5116982A (en) * | 1990-08-06 | 1992-05-26 | Dowelanco | Preparation of fluorohalophenols and n-acyfluorohaloanilines |
| US5288930A (en) * | 1991-08-02 | 1994-02-22 | Imperial Chemical Industries Plc | Purification of 1,1,1,2-tetrafluoroethane |
-
1994
- 1994-09-14 US US08/305,626 patent/US5552533A/en not_active Expired - Lifetime
-
1995
- 1995-08-29 TW TW084108990A patent/TW296381B/zh active
- 1995-09-05 AU AU35008/95A patent/AU3500895A/en not_active Abandoned
- 1995-09-05 WO PCT/US1995/011098 patent/WO1996008502A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4514562A (en) * | 1981-11-27 | 1985-04-30 | Pierrel Spa | Fluorinated erythromycin compounds and a process for preparation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016023178A (ja) * | 2014-07-24 | 2016-02-08 | 国立大学法人 名古屋工業大学 | フルオロマロン酸エステル誘導体の製造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| US5552533A (en) | 1996-09-03 |
| TW296381B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1997-01-21 |
| AU3500895A (en) | 1996-03-29 |
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