FI67073C - Foerfarande foer framstaellning av terapeutiskt anvaendbara cironsyraderivat och motsvarande treo-beta-laktoner - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara cironsyraderivat och motsvarande treo-beta-laktoner Download PDFInfo
- Publication number
- FI67073C FI67073C FI793976A FI793976A FI67073C FI 67073 C FI67073 C FI 67073C FI 793976 A FI793976 A FI 793976A FI 793976 A FI793976 A FI 793976A FI 67073 C FI67073 C FI 67073C
- Authority
- FI
- Finland
- Prior art keywords
- acid
- threo
- formula
- lactone
- citric acid
- Prior art date
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- 239000002253 acid Substances 0.000 claims description 73
- 150000003839 salts Chemical class 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 25
- 229910052751 metal Inorganic materials 0.000 claims description 18
- 239000002184 metal Substances 0.000 claims description 18
- GTZCVFVGUGFEME-HNQUOIGGSA-N trans-aconitic acid Chemical compound OC(=O)C\C(C(O)=O)=C/C(O)=O GTZCVFVGUGFEME-HNQUOIGGSA-N 0.000 claims description 15
- PLYZXLXZNMQAAU-DZSWIPIPSA-N (1r,2r)-1-chloro-2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)C[C@@](O)(C(O)=O)[C@@H](Cl)C(O)=O PLYZXLXZNMQAAU-DZSWIPIPSA-N 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- 229910052783 alkali metal Inorganic materials 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 9
- 229910001514 alkali metal chloride Inorganic materials 0.000 claims description 8
- 239000003125 aqueous solvent Substances 0.000 claims description 8
- 125000003180 beta-lactone group Chemical group 0.000 claims description 8
- 150000001860 citric acid derivatives Chemical class 0.000 claims description 7
- 239000003513 alkali Substances 0.000 claims description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- GTZCVFVGUGFEME-IWQZZHSRSA-N cis-aconitic acid Chemical compound OC(=O)C\C(C(O)=O)=C\C(O)=O GTZCVFVGUGFEME-IWQZZHSRSA-N 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910001617 alkaline earth metal chloride Inorganic materials 0.000 claims description 3
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229910000462 iron(III) oxide hydroxide Inorganic materials 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 2
- WBLXMRIMSGHSAC-UHFFFAOYSA-N [Cl].[Cl] Chemical compound [Cl].[Cl] WBLXMRIMSGHSAC-UHFFFAOYSA-N 0.000 claims 1
- 239000003599 detergent Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 29
- 229960004106 citric acid Drugs 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- GTZCVFVGUGFEME-UHFFFAOYSA-N trans-aconitic acid Natural products OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 0.000 description 13
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 238000006735 epoxidation reaction Methods 0.000 description 7
- QTDBPWPSHBVVMQ-UHFFFAOYSA-N ethyl acetate;tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl.CCOC(C)=O QTDBPWPSHBVVMQ-UHFFFAOYSA-N 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- 239000011707 mineral Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- -1 alkali metal salt Chemical class 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Inorganic materials Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 150000004682 monohydrates Chemical class 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000001124 (E)-prop-1-ene-1,2,3-tricarboxylic acid Substances 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 229940091181 aconitic acid Drugs 0.000 description 3
- 229960002303 citric acid monohydrate Drugs 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 235000012631 food intake Nutrition 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- IBOFVQJTBBUKMU-UHFFFAOYSA-N 4,4'-methylene-bis-(2-chloroaniline) Chemical compound C1=C(Cl)C(N)=CC=C1CC1=CC=C(N)C(Cl)=C1 IBOFVQJTBBUKMU-UHFFFAOYSA-N 0.000 description 2
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical group 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 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- SATVIFGJTRRDQU-UHFFFAOYSA-N potassium hypochlorite Chemical compound [K+].Cl[O-] SATVIFGJTRRDQU-UHFFFAOYSA-N 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- RJWRPTUYTNTXIR-UHFFFAOYSA-N (2-methyl-4-nitrophenyl)methanamine;hydrochloride Chemical compound Cl.CC1=CC([N+]([O-])=O)=CC=C1CN RJWRPTUYTNTXIR-UHFFFAOYSA-N 0.000 description 1
- CZQQGVFHLSBEDV-UHFFFAOYSA-N 1-(4-nitrophenyl)ethylazanium;chloride Chemical compound Cl.CC(N)C1=CC=C([N+]([O-])=O)C=C1 CZQQGVFHLSBEDV-UHFFFAOYSA-N 0.000 description 1
- PLYZXLXZNMQAAU-UHFFFAOYSA-N 1-chloro-2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)C(Cl)C(O)=O PLYZXLXZNMQAAU-UHFFFAOYSA-N 0.000 description 1
- FMJUDUJLTNVWCH-UHFFFAOYSA-N 2-ethoxy-3-(4-hydroxyphenyl)propanoic acid Chemical compound CCOC(C(O)=O)CC1=CC=C(O)C=C1 FMJUDUJLTNVWCH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QWMFKVNJIYNWII-UHFFFAOYSA-N 5-bromo-2-(2,5-dimethylpyrrol-1-yl)pyridine Chemical compound CC1=CC=C(C)N1C1=CC=C(Br)C=N1 QWMFKVNJIYNWII-UHFFFAOYSA-N 0.000 description 1
- NASQAPCVYLOLIN-UHFFFAOYSA-N CC1(CC=C(C=C1)CN)[N+](=O)[O-] Chemical compound CC1(CC=C(C=C1)CN)[N+](=O)[O-] NASQAPCVYLOLIN-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- ZMJBYMUCKBYSCP-UHFFFAOYSA-N Hydroxycitric acid Chemical compound OC(=O)C(O)C(O)(C(O)=O)CC(O)=O ZMJBYMUCKBYSCP-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- MKRHJYCNUVGFSZ-UHFFFAOYSA-N OC(C(=O)O)C(O)(C(=O)O)CC(=O)O.C(CC(O)(C(=O)O)CC(=O)O)(=O)O Chemical compound OC(C(=O)O)C(O)(C(=O)O)CC(=O)O.C(CC(O)(C(=O)O)CC(=O)O)(=O)O MKRHJYCNUVGFSZ-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- VYORQDFEXHAUJW-UHFFFAOYSA-N [Na].ClCC(=O)O.[Na] Chemical compound [Na].ClCC(=O)O.[Na] VYORQDFEXHAUJW-UHFFFAOYSA-N 0.000 description 1
- 229940023019 aconite Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 230000000578 anorexic effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 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
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229940089491 hydroxycitric acid Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- GIZSHQYTTBQKOQ-UHFFFAOYSA-N threo-Syringoylglycerol Chemical compound COC1=CC(C(O)C(O)CO)=CC(OC)=C1O GIZSHQYTTBQKOQ-UHFFFAOYSA-N 0.000 description 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
- CMPGARWFYBADJI-UHFFFAOYSA-L tungstic acid Chemical compound O[W](O)(=O)=O CMPGARWFYBADJI-UHFFFAOYSA-L 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/02—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D305/10—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings having one or more double bonds between ring members or between ring members and non-ring members
- C07D305/12—Beta-lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/363—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
- C07C59/295—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/48—Compounds containing oxirane rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Epoxy Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97350478 | 1978-12-26 | ||
| US05/973,504 US4312885A (en) | 1978-12-26 | 1978-12-26 | Chlorocitric acids |
| CH1058079 | 1979-11-28 | ||
| CH1058079 | 1979-11-28 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI793976A7 FI793976A7 (fi) | 1980-06-27 |
| FI67073B FI67073B (fi) | 1984-09-28 |
| FI67073C true FI67073C (fi) | 1985-01-10 |
Family
ID=25706941
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI793976A FI67073C (fi) | 1978-12-26 | 1979-12-18 | Foerfarande foer framstaellning av terapeutiskt anvaendbara cironsyraderivat och motsvarande treo-beta-laktoner |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0016867B1 (da) |
| AR (1) | AR222201A1 (da) |
| AU (1) | AU527139B2 (da) |
| CA (1) | CA1138470A (da) |
| DE (1) | DE2965783D1 (da) |
| DK (1) | DK154641C (da) |
| ES (2) | ES8100243A1 (da) |
| FI (1) | FI67073C (da) |
| HU (1) | HU179987B (da) |
| IE (1) | IE49341B1 (da) |
| IL (1) | IL59015A (da) |
| MC (1) | MC1299A1 (da) |
| NO (1) | NO153491C (da) |
| NZ (1) | NZ192423A (da) |
| PH (1) | PH14915A (da) |
| PT (1) | PT70628A (da) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT500800B1 (de) | 2004-09-08 | 2008-07-15 | Biomedica Medizinprodukte Gmbh | Verfahren zur bestimmung von probnp |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3356721A (en) * | 1962-03-21 | 1967-12-05 | Richard H Wiley | Citric acid manufacture |
| US3764692A (en) * | 1970-09-30 | 1973-10-09 | Hoffmann La Roche | Method of treating obesity |
| US3901915A (en) * | 1973-10-10 | 1975-08-26 | Hoffmann La Roche | Optical resolution of organic carboxylic acids |
| US4123458A (en) * | 1975-12-22 | 1978-10-31 | Lever Brothers Company | Preparation of cis and trans aconitic acids and their salts |
-
1979
- 1979-12-17 NZ NZ192423A patent/NZ192423A/xx unknown
- 1979-12-18 FI FI793976A patent/FI67073C/fi not_active IP Right Cessation
- 1979-12-19 CA CA000342235A patent/CA1138470A/en not_active Expired
- 1979-12-19 MC MC791421A patent/MC1299A1/fr unknown
- 1979-12-19 AU AU54009/79A patent/AU527139B2/en not_active Ceased
- 1979-12-20 IL IL7959015A patent/IL59015A/xx unknown
- 1979-12-21 EP EP79105314A patent/EP0016867B1/de not_active Expired
- 1979-12-21 HU HU79HO2203A patent/HU179987B/hu not_active IP Right Cessation
- 1979-12-21 PT PT70628A patent/PT70628A/pt unknown
- 1979-12-21 NO NO79794232A patent/NO153491C/no unknown
- 1979-12-21 PH PH23453A patent/PH14915A/en unknown
- 1979-12-21 DE DE7979105314T patent/DE2965783D1/de not_active Expired
- 1979-12-21 DK DK554079A patent/DK154641C/da not_active IP Right Cessation
- 1979-12-21 IE IE2501/79A patent/IE49341B1/en unknown
- 1979-12-24 ES ES79487247A patent/ES8100243A1/es not_active Expired
-
1980
- 1980-06-25 ES ES492727A patent/ES8105252A1/es not_active Expired
- 1980-10-26 AR AR279443A patent/AR222201A1/es active
Also Published As
| Publication number | Publication date |
|---|---|
| NO153491C (no) | 1986-04-02 |
| AU5400979A (en) | 1980-07-03 |
| IL59015A (en) | 1983-10-31 |
| IE49341B1 (en) | 1985-09-18 |
| IE792501L (en) | 1980-06-26 |
| ES492727A0 (es) | 1981-06-01 |
| DK154641B (da) | 1988-12-05 |
| AR222201A1 (es) | 1981-04-30 |
| PT70628A (en) | 1980-01-01 |
| FI67073B (fi) | 1984-09-28 |
| NO794232L (no) | 1980-06-27 |
| ES8105252A1 (es) | 1981-06-01 |
| CA1138470A (en) | 1982-12-28 |
| EP0016867B1 (de) | 1983-06-22 |
| FI793976A7 (fi) | 1980-06-27 |
| NZ192423A (en) | 1981-12-15 |
| EP0016867A1 (de) | 1980-10-15 |
| MC1299A1 (fr) | 1980-10-03 |
| DK554079A (da) | 1980-06-27 |
| ES487247A0 (es) | 1980-11-01 |
| NO153491B (no) | 1985-12-23 |
| PH14915A (en) | 1982-01-29 |
| ES8100243A1 (es) | 1980-11-01 |
| AU527139B2 (en) | 1983-02-17 |
| DK154641C (da) | 1989-05-08 |
| HU179987B (en) | 1983-01-28 |
| DE2965783D1 (en) | 1983-07-28 |
| IL59015A0 (en) | 1980-03-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: F. HOFFMANN-LA ROCHE AG |