DK159446B - Fremgangsmaade til fremstilling af oxazolinoazetidinylhydroxymethylbutensyrederivater - Google Patents
Fremgangsmaade til fremstilling af oxazolinoazetidinylhydroxymethylbutensyrederivater Download PDFInfo
- Publication number
- DK159446B DK159446B DK179183A DK179183A DK159446B DK 159446 B DK159446 B DK 159446B DK 179183 A DK179183 A DK 179183A DK 179183 A DK179183 A DK 179183A DK 159446 B DK159446 B DK 159446B
- Authority
- DK
- Denmark
- Prior art keywords
- acid
- process according
- alkyl
- group
- oxazolinoazetidinyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 13
- BAOHMJZBCIUQEO-UHFFFAOYSA-N 2-(hydroxymethyl)but-2-enoic acid Chemical class CC=C(CO)C(O)=O BAOHMJZBCIUQEO-UHFFFAOYSA-N 0.000 title 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 230000003647 oxidation Effects 0.000 claims description 9
- 238000007254 oxidation reaction Methods 0.000 claims description 9
- SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 150000005826 halohydrocarbons Chemical class 0.000 claims description 3
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 claims description 2
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 claims description 2
- LBAYFEDWGHXMSM-UHFFFAOYSA-N butaneperoxoic acid Chemical compound CCCC(=O)OO LBAYFEDWGHXMSM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- CZPZWMPYEINMCF-UHFFFAOYSA-N propaneperoxoic acid Chemical compound CCC(=O)OO CZPZWMPYEINMCF-UHFFFAOYSA-N 0.000 claims description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims 2
- JREGFGVDTJQHBT-UHFFFAOYSA-N 2-(iodomethyl)butanoic acid Chemical class CCC(CI)C(O)=O JREGFGVDTJQHBT-UHFFFAOYSA-N 0.000 claims 1
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 claims 1
- -1 iodide methylbutanoic acid derivative Chemical class 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 19
- 150000002148 esters Chemical class 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229910001516 alkali metal iodide Inorganic materials 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 231100000989 no adverse effect Toxicity 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- JHNRZXQVBKRYKN-VQHVLOKHSA-N (ne)-n-(1-phenylethylidene)hydroxylamine Chemical compound O\N=C(/C)C1=CC=CC=C1 JHNRZXQVBKRYKN-VQHVLOKHSA-N 0.000 description 1
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- ZMZQVAUJTDKQGE-UHFFFAOYSA-N 2-ethylhydracrylic acid Chemical class CCC(CO)C(O)=O ZMZQVAUJTDKQGE-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 239000004287 Dehydroacetic acid Substances 0.000 description 1
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- URQPRGSODZZBBN-OBTVHEKISA-N benzhydryl (2r)-3-(iodomethyl)-2-[(1r,5s)-7-oxo-3-phenyl-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl]but-3-enoate Chemical compound O([C@@H]1N(C([C@@H]1N=1)=O)[C@H](C(=C)CI)C(=O)OC(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C1=CC=CC=C1 URQPRGSODZZBBN-OBTVHEKISA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- JEQRBTDTEKWZBW-UHFFFAOYSA-N dehydroacetic acid Chemical compound CC(=O)C1=C(O)OC(C)=CC1=O JEQRBTDTEKWZBW-UHFFFAOYSA-N 0.000 description 1
- 229940061632 dehydroacetic acid Drugs 0.000 description 1
- PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 description 1
- 235000019258 dehydroacetic acid Nutrition 0.000 description 1
- 125000006182 dimethyl benzyl group Chemical group 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- QFWPJPIVLCBXFJ-UHFFFAOYSA-N glymidine Chemical compound N1=CC(OCCOC)=CN=C1NS(=O)(=O)C1=CC=CC=C1 QFWPJPIVLCBXFJ-UHFFFAOYSA-N 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 239000004434 industrial solvent Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000006178 methyl benzyl group Chemical group 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- NALMPLUMOWIVJC-UHFFFAOYSA-N n,n,4-trimethylbenzeneamine oxide Chemical compound CC1=CC=C([N+](C)(C)[O-])C=C1 NALMPLUMOWIVJC-UHFFFAOYSA-N 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000002978 peroxides Chemical group 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000015281 sodium iodate Nutrition 0.000 description 1
- 239000011697 sodium iodate Substances 0.000 description 1
- 229940032753 sodium iodate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
i
DK 159446 B
Den foreliggende opfindelse angår en fremgangsmåde til fremstilling af et oxazolinoazetidinylhydroxymethylbutensyrederivat med formel (II)
R
5 0 \ '
T-f CH
1 ii ^
Qss>-NCHCCH OH
ld
. COOR
(II) 10 hvori R betegner en al kyl-, aralkyl- eller arylgruppe, og R1 betegner et hydrogenatom eller en carboxybeskyttende gruppe, hvilken fremgangsmåde er ejendommelig ved, at man oxiderer det tilsvarende oxazolinoazetidi-nyliodmethylbutensyrederivat med formel (I)
R
/ \_; ch ί II ^
os5i-NCHCCH2-I
000R1 il) 20 hvori R og R1 har den ovenfor anførte betydning, med en percarboxylsyre eller et salt deraf.
Kendte fremgangsmåder til omdannelse af en halogenmethylforbindel se til en hydroxymethyl forbi ndel se benytter i almindelighed hydrolyse af 25 den tilsvarende iodmethylforbindelse. Det er ligeledes kendt at fremstille en hydroxymethyl forbi ndel se ved omsætning af den tilsvarende iodmethylforbindelse med et tungmetalsalt, jvf. DE-A-2.800.860.
Det har nu vist sig, at omdannelsen af halogenmethylforbi ndel sen til hydroxymethyl forbindel sen forløber mere økonomisk og med højere ud- 30 bytte ved oxygenering, og den foreliggende opfindelse er baseret på denne erkendelse.
Det er kendt, at produkterne (II), der fås ved denne fremgangsmåde, er værdifulde som mellemprodukter ved fremstilling af værdifulde materialer, f.eks. antibakteriel le midler af oxacephemtype (se f.eks. M.
35 Yoshioka et al., Tetrahedron Letters, bind 21, pp. 351-354 (1980)).
Alkyl-, aralkyl- eller arylgruppen R har fortrinsvis 1-12 carbon-atomer og kan være substitueret med en gruppe, som ikke har nogen ugunstig virkning under reaktionsbetingelserne ved fremgangsmåden ifølge op-
DK 159446 B
2 findelsen, f.eks. Cj-Cg-alkyl-, nitro, Cj-Cg-alkoxy, monocyklisk aryloxy, halogen eller lignende.
Den carboxybeskyttende gruppe R1 kan være en esterdannende gruppe ' til beskyttelse af carboxygruppen under de anvendte reaktionsbetingel-5 ser. Foretrukne R^-grupper er lette at fjerne uden ugunstig virkning på produktet (II) efter reaktionen ifølge opfindelsen, når dette ønskes.
Repræsentative R^-grupper indeholder 1-20 carbonatomer og er velkendte inden for kemien vedrørende anti bakteriel le midler af jS-lactam-type, og de indbefatter grupper, som danner al kyl estere, f.eks. t-10 butyl-, cyclopropylmethyl-, ally!- eller 2,2,2-trichlorethyl estere; aralkyl estere, f.eks. benzyl-, methyl benzyl-, dimethyl benzyl -, methoxybenzyl-, ethoxybenzyl-, nitrobenzyl-, aminobenzyl -,-diphenylmethyl-, phthalidyl- eller phenacylestere; arylestere, f.eks. phenyl-, pentachlorphenyl- eller indanylestere; estere med en N-15 hydroxyaminoforbindelse, f.eks. en ester med acetoneoxim, acetophenonoxim, acetaldoxim, N-hydroxysuccinimid eller N-hydroxyphthalimid; eller de kan erstattes med en gruppe, som danner et ~ syreanhydrid med carbonsyre eller en carboxylsyre eller en amidgruppe.
Disse R*-grupper kan yderligere være substitueret med en gruppe, 20 som ikke har nogen ugunstig virkning på reaktionen ifølge opfindelsen, og kan være sådanne, som er eksemplificeret ovenfor i relation til R-gruppen.
De ovenfor definerede udgangsforbindelser (I) er kendte eller analoge med forbindelser beskrevet i den citerede Yoshioka et al. publika-25 ti on eller anden litteratur vedrørende /Mactam kemi.
Som anført ovenfor vedrører opfindelsen erstatning af halogen med hydroxy under indvirkning af et oxidationsreagens. Reaktionsforløbene illustreres nedenfor ved reaktionsskemaet 30
R R
Nssss'-'-O —O
X\ 1 \ j
\_/ CEL Percarboxylsyre \_; CEL
i ii 2 _^^ [ II 2
_NCHCCH2'I 7 ^-NCHCCH20H
35 (I) 000r1 (ii) 000r1 hvori R og R^ har den ovenfor definerede betydning.
Oxidationsreagenset kan være en percarboxylsyre eller et salt der- DK 159446 3 af. Reaktionen mentes først at være en peroxidsubstitution som anført senere, men menes nu at forløbe ad en anden oxidationsmekanismerute direkte fra forbindelse (I) til (II).
Ved percarboxylsyreoxidationsforløbet oxideres forbindelsen (I) 5 med en percarboxylsyre eller et salt deraf, f.eks. pereddikesyre, per-propionsyre, persmørsyre, monoperphthalsyre, perbenzoesyre, m-chlorper-benzoesyre eller et salt deraf.
Selv om det endnu ikke er blevet videnskabeligt bevist, menes det nu, at reaktionsforløbet går via oxidation af iodet til en iodosogruppe, 10 hvorefter der sker en omlejring til hypoiodid og efterfølgende oxidation til i odat, og automatisk hydrolyse giver alkoholen (II) og iodsyre. Dette reaktionsforløb anses for at være hidtil ukendt.
Reaktionen kan udføres i et inert industrielt opløsningsmiddel, f.eks. et vand-, carbonhydrid-, halogencarbonhydrid-, keton-, ester-, 15 amid- eller al kohol opløsningsmiddel eller en blanding af disse. For eksempel kan opløsningsmidlet være benzen, dichlormethan, chloroform, car-bontetrachlorid, acetone, methyl ethyl keton, methyl isobutylketon, cyclo-pentanon, cyclohexanon, ethyl acetat, ethylcarbonat, ethylencarbonat, N,N-dimethylformamid, hexamethylphosphortriamid, 1-ethylpyrrolidin-2-on, 20 1,3-dimethylimidazolidin-2-on, acetonitril, benzonitril, dimethylsulf-oxid, isopropanol, ethanol, methanol, vand eller en blanding af disse.
Blandt disse foretrækkes især vand-, halogencarbonhydrid- og esteropløsningsmidler, f.eks. vand, ethylacetat, dichlormethan, chloroform eller carbontetrachlorid.
25 Reaktionen kan accelereres med en base, fortrinsvis en uorganisk base, f.eks. al kalimetalcarbonat eller -hydrogencarbonat til opfangning af den under reaktionen dannede i odsyre. Desuden kan reaktionen fortrinsvis udføres i et medium bestående af to faser, f.eks. lag af vand og et opløsningsmiddel, som er ublandbart med vand. Sidstnævnte fase 30 tjener til opløsning af det under reaktionen dannede uorganiske salt. Tungtopløselige salte fælder ud som fast stof, når mængden af det vandige lag er tilstrækkelig lille. Det vandige lag kan også tjene til opløsning af basen, som tilsættes. Natri umiodat, som er fremstillet under reaktionen, kan fjernes ved ren og skær filtrering.
35 Udgangsmaterialet (I) kan fremstilles ud fra den tilsvarende chlor-eller bromforbindelse ved behandling med et alkalimetaliodid på konventionel måde inden for området, dvs. ved opløsning af udgangsmaterialet og et alkalimetaliodid i et polært opløsningsmiddel. I dette tilfælde
4 DK 159446 B
kan den i reaktionsblandingén frembragte forbindelse (I) anvendes direkte til percarboxylsyreoxidationen uden isolering.
Reaktionsblandingen kan oparbejdes på konventionel måde og give > produktet (II) i højt udbytte. Sådanne metoder til isolering og rensning 5 indbefatter ekstraktion, vask, tørring, filtrering, koncentrering, kromatografi, adsorption, eluering, fordelingsadskillelse og omkrystallisa-tion.
Opfindelsen beskrives nærmere i det følgende ved eksempler. I tabellerne anvendes følgende forkortelser: 1°
Ac = acetyl BH = di phenylmethyl DHa = dehydroeddikesyre ækv. = ækvivalent
Et = ethyl m-CPBA = m-chlorperbenzoesyre
St = stuetemperatur Ph = phenyl 15 THF = tetrahydrofuran temp = temperatur
Eksempel 1
Ph. Pk
20 N-J—O
W f2 -> H ^
_NCHCCH^I 0^j-N? HCCH20H
^ 000CHPh2 000CHPh2 25
Til en blanding af (2R)-2-[(lR,5S)-3-phenyl-7-oxo-4-oxa-2,6-diaza-bicyclo[3.2.0]hept-2-en-6-yl]-3-iodmethyl-3-butensyre-diphenylmethyl-ester (1) i et organisk opløsningsmiddel og uorganisk base i vand sættes portionsvis en persyre under nitrogengas, og blandingen omrøres i det 30 anførte tidsrum ved den anførte temperatur under nitrogen. Reaktionsblandingen vaskes med vand, vandig 5% natriumthi osul fat, vandig natrium-hydrogencarbonat og vand, tørres over natriumsulfat og koncentreres under reduceret tryk. Remanensen omkrystalliseres i ethanol, hvorved (2R)-2-[(lR,5S)-3-phenyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl]-35 3-hydroxymethyl-3-butensyre-diphenylmethyl ester (2) fås. Snip. 100-104°C.
Reaktionsbetingelserne er sammenstil!et i tabel (I).
DK 159446 B
5 O) +j •P *—s >ιο\ο oo cm h i co j· η η O i i jg w COOOiN I 00 00 ON d\ !> i i 3 in
-H -p CMHCMHC"NCM !>i>!>OCM
.jj n—' iH <M
Λ--' O ' gu .pH-pO-P-P-P-P-P-P0 (DO CQ I 01 -=*" CQ 0} CQ CO CQ 01 •P ^ 1Λ
g H
ω o) n m \ o \ m3 η h g <t3 o\\>-mhcmhh\\
o "d+J \ H \ ·· \ .. \ H
p_i g 01 ..CM ·· Η ·· O ·· τ-( H \ \
g g !> WwCViwCVlHH^w^HH
H S-d θ' °C\i θ' CM O* O O CM CM CM H
O £ ,-J CM g W K CM CM CM g g ' § U ΐ \ ΐ ΜΗ >> « « s Q.(H o cm o o o o o cm cm g fa g 0 kGhq&imhoo^h
PM
§ S^OinOOOOOOO
pj ^ CM CM CM CM CM CM CM CM ΓΊ CM lfN
m S! s '"“n Ίη W W <r\ <r\ <r\ m W 3 O O OOOOOc^m
ri η'ωοο O O O O O O O
ri Λ1 g w w E s tg w o'O
g dd'iddoJaSd. cviE
En
H
m ^ s ® H e s ___ S 'q' or^OicnOOOOO^
o° aii li si ^ sT
<D <·<!<! S3 U n cn π π π H mmpQffl c-λ o o o o o o <. >n * CL|CMCM(1|0000000
ri g > o o o o o ffi jr* tP hT
H P .¾ I i i i g I g g g 33 g gj iéeHPMOooouo Éh
Eksempel 2 6
DK 159446 B
I · R
5 \-j ch2 _ \_/ CH
qJ—^^bS^i JZ1choch,oh (!) C00R (2) éOOR1 10 På tilsvarende måde som i eksempel 1 oxideres (2R)-2-[(lR,5S)-3-R- 7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl]-3-iodmethyl-3-buten-syre-R^-ester (1) til frembringelse af (2R)-2-[(lR,5S)-3-R-7-oxo-4-oxa-2,6-diazabi cyclo[3.2.0]hept-2-en-6-yl]-3-hydroxymethyl-3-butensyre-R1-ester (2).
15 R = p-tolyl, R1 = diphenylmethyl, smp. 124-126°C.
R = benzyl, R1 = t-butyl, smp. 85-87°C.
Claims (6)
1. Fremgangsmåde til fremstilling af et oxazolinoazetidinylhydroxymethyl butensyrederi vat med formel (II) R 5 Ν-ξΞ-~—O \_/ ch ί || 2 _NCHCCH OH (ii) ^oor1 10 hvori R betegner en alkyl-, aralkyl- eller arylgruppe, og R1 betegner et hydrogenatom eller en carboxybeskyttende gruppe, KENDETEGNET ved, AT man oxiderer det tilsvarende oxazolinoazetidinyliodmethylbutensyrederivat med formel (I) 15 r π' CH II 2 _^CHCCH2'I . 20 (I) *00Rl hvori R og R1 har den ovenfor anførte betydning, med en percarboxylsyre eller et salt deraf.
2. Fremgangsmåde ifølge krav 1, KENDETEGNET ved, AT R betegner en 25 alkyl-, aralkyl- eller arylgruppe med 1-12 carbonatomer, der eventuelt -er substitueret med en gruppe i form af Cj-i^-alkyl, nitro, Cj-t^-alko-xy, monocyklisk aryloxy eller halogen.
3. Fremgangsmåde ifølge krav 1 eller 2, KENDETEGNET ved, AT R1 betegner en al kyl-, aralkyl- eller arylester-dannende gruppe med 1-20 car-30 bonatomer.
4. Fremgangsmåde ifølge et eller flere af de foregående krav, KENDETEGNET ved, AT percarboxylsyren er udvalgt blandt pereddikesyre, per-propionsyre, persmørsyre, monoperphthalsyre, perbenzoesyre, m-chlorper-benzoesyre og salte deraf, samt hydrogenperoxid i nærværelse af en lave-35 re alkansyre.
5. Fremgangsmåde ifølge et eller flere af de foregående krav, KENDETEGNET ved, AT oxidationen udføres i et vand-, halogencarbonhydrid-eller esteropløsningsmiddel. DK 159446 B 8
6. Fremgangsmåde ifølge et eller flere af de foregående krav, KENDETEGNET ved, AT oxidationen accelereres med en base eller med et medium bestående af faser af vand og opløsningsmiddel, der er ublandbart med vand. 5 10 15
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6940282 | 1982-04-23 | ||
| JP57069402A JPS58185588A (ja) | 1982-04-23 | 1982-04-23 | 空気酸化によるハロメチル化合物の酸化方法および酸化生成物 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK179183D0 DK179183D0 (da) | 1983-04-22 |
| DK179183A DK179183A (da) | 1983-10-24 |
| DK159446B true DK159446B (da) | 1990-10-15 |
| DK159446C DK159446C (da) | 1991-03-18 |
Family
ID=13401568
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK179183A DK159446C (da) | 1982-04-23 | 1983-04-22 | Fremgangsmaade til fremstilling af oxazolinoazetidinylhydroxymethylbutensyrederivater |
| DK032390A DK162768C (da) | 1982-04-23 | 1990-02-07 | Fremgangsmaade til fremstilling af oxazolinoazetidinylhydroxymethylbutensyrederivater |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK032390A DK162768C (da) | 1982-04-23 | 1990-02-07 | Fremgangsmaade til fremstilling af oxazolinoazetidinylhydroxymethylbutensyrederivater |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4581173A (da) |
| EP (2) | EP0093907B1 (da) |
| JP (1) | JPS58185588A (da) |
| KR (1) | KR890000032B1 (da) |
| AU (1) | AU553611B2 (da) |
| CA (1) | CA1194878A (da) |
| DE (1) | DE3370334D1 (da) |
| DK (2) | DK159446C (da) |
| GB (1) | GB2120241B (da) |
| GR (1) | GR78513B (da) |
| HU (1) | HU193038B (da) |
| IE (1) | IE55307B1 (da) |
| IL (1) | IL68475A (da) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8067650B2 (en) | 2006-08-24 | 2011-11-29 | Honeywell International Inc. | Process for the production of HFO trans-1234ze from HFC-245fa |
| US7485760B2 (en) | 2006-08-24 | 2009-02-03 | Honeywell International Inc. | Integrated HFC trans-1234ze manufacture process |
| CN116496298A (zh) * | 2023-05-04 | 2023-07-28 | 深圳六合六医疗器械有限公司 | 一锅法制备氟氧头孢中间体的方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1090806A (en) * | 1977-01-10 | 1980-12-02 | Mitsuru Yoshioka | Oxazolines |
| GB1557552A (en) * | 1977-02-15 | 1979-12-12 | Shionogi & Co | 1 oxadethiacepham compounds |
-
1982
- 1982-04-23 JP JP57069402A patent/JPS58185588A/ja active Granted
-
1983
- 1983-04-07 US US06/482,974 patent/US4581173A/en not_active Expired - Lifetime
- 1983-04-12 GR GR71064A patent/GR78513B/el unknown
- 1983-04-14 KR KR1019830001558A patent/KR890000032B1/ko not_active Expired
- 1983-04-20 EP EP83103863A patent/EP0093907B1/en not_active Expired
- 1983-04-20 EP EP85107298A patent/EP0180709B1/en not_active Expired
- 1983-04-20 DE DE8383103863T patent/DE3370334D1/de not_active Expired
- 1983-04-20 GB GB08310691A patent/GB2120241B/en not_active Expired
- 1983-04-21 IE IE912/83A patent/IE55307B1/en not_active IP Right Cessation
- 1983-04-22 DK DK179183A patent/DK159446C/da not_active IP Right Cessation
- 1983-04-22 AU AU13878/83A patent/AU553611B2/en not_active Expired
- 1983-04-22 HU HU831405A patent/HU193038B/hu unknown
- 1983-04-22 IL IL68475A patent/IL68475A/xx not_active IP Right Cessation
- 1983-04-25 CA CA000426670A patent/CA1194878A/en not_active Expired
-
1990
- 1990-02-07 DK DK032390A patent/DK162768C/da not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| GB2120241A (en) | 1983-11-30 |
| DK162768C (da) | 1992-04-27 |
| KR890000032B1 (ko) | 1989-03-06 |
| EP0093907A1 (en) | 1983-11-16 |
| IL68475A (en) | 1987-01-30 |
| IL68475A0 (en) | 1983-07-31 |
| US4581173A (en) | 1986-04-08 |
| JPH0242835B2 (da) | 1990-09-26 |
| DK159446C (da) | 1991-03-18 |
| KR840004433A (ko) | 1984-10-15 |
| DK32390D0 (da) | 1990-02-07 |
| GR78513B (da) | 1984-09-27 |
| DK162768B (da) | 1991-12-09 |
| EP0180709A1 (en) | 1986-05-14 |
| DK32390A (da) | 1990-02-07 |
| AU1387883A (en) | 1983-10-27 |
| IE55307B1 (en) | 1990-08-01 |
| DK179183A (da) | 1983-10-24 |
| AU553611B2 (en) | 1986-07-24 |
| EP0180709B1 (en) | 1989-02-22 |
| GB2120241B (en) | 1985-05-09 |
| GB8310691D0 (en) | 1983-05-25 |
| DK179183D0 (da) | 1983-04-22 |
| HU193038B (en) | 1987-08-28 |
| EP0093907B1 (en) | 1987-03-18 |
| CA1194878A (en) | 1985-10-08 |
| IE830912L (en) | 1983-10-23 |
| DE3370334D1 (en) | 1987-04-23 |
| JPS58185588A (ja) | 1983-10-29 |
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