WO2021117053A1 - An improved process for preparation of pure aldoxime - Google Patents
An improved process for preparation of pure aldoxime Download PDFInfo
- Publication number
- WO2021117053A1 WO2021117053A1 PCT/IN2020/050704 IN2020050704W WO2021117053A1 WO 2021117053 A1 WO2021117053 A1 WO 2021117053A1 IN 2020050704 W IN2020050704 W IN 2020050704W WO 2021117053 A1 WO2021117053 A1 WO 2021117053A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- oxime
- aldoxime
- solution
- benzaldehyde
- aldehyde
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 63
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims abstract description 68
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 39
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 33
- -1 anisaldehyde oxime Chemical class 0.000 claims description 27
- 150000001299 aldehydes Chemical class 0.000 claims description 19
- 239000011541 reaction mixture Substances 0.000 claims description 19
- 150000002923 oximes Chemical class 0.000 claims description 16
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 claims description 14
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 14
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 14
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 14
- ZRSNZINYAWTAHE-UHFFFAOYSA-N Anisaldehyde Natural products COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 claims description 12
- MTFJSAGADRTKCI-VMPITWQZSA-N chembl77510 Chemical compound O\N=C\C1=CC=CC=N1 MTFJSAGADRTKCI-VMPITWQZSA-N 0.000 claims description 12
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 11
- 238000012545 processing Methods 0.000 claims description 11
- JIVGSHFYXPRRSZ-UHFFFAOYSA-N 2,3-dimethoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1OC JIVGSHFYXPRRSZ-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 150000001350 alkyl halides Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 239000000412 dendrimer Substances 0.000 claims description 7
- 229920000736 dendritic polymer Polymers 0.000 claims description 7
- 150000004820 halides Chemical group 0.000 claims description 7
- POCUPXSSKQAQRY-UHFFFAOYSA-N hydroxylamine;hydrate Chemical compound O.ON POCUPXSSKQAQRY-UHFFFAOYSA-N 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 7
- 150000004032 porphyrins Chemical class 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 claims description 6
- YBKOPFQCLSPTPV-VMPITWQZSA-N 3-pyridine aldoxime Chemical compound O\N=C\C1=CC=CN=C1 YBKOPFQCLSPTPV-VMPITWQZSA-N 0.000 claims description 6
- QKWBTCRVPQHOMT-UITAMQMPSA-N (nz)-n-[(4-chlorophenyl)methylidene]hydroxylamine Chemical compound O\N=C/C1=CC=C(Cl)C=C1 QKWBTCRVPQHOMT-UITAMQMPSA-N 0.000 claims description 5
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 claims description 5
- GASLBPLHYRZLLT-GQCTYLIASA-N (ne)-n-(thiophen-2-ylmethylidene)hydroxylamine Chemical compound O\N=C\C1=CC=CS1 GASLBPLHYRZLLT-GQCTYLIASA-N 0.000 claims description 4
- GKAIQNACVNFHCU-UXBLZVDNSA-N (ne)-n-[(2,3-dimethoxyphenyl)methylidene]hydroxylamine Chemical compound COC1=CC=CC(\C=N\O)=C1OC GKAIQNACVNFHCU-UXBLZVDNSA-N 0.000 claims description 4
- FZIVKDWRLLMSEJ-UITAMQMPSA-N (nz)-n-[(2-chlorophenyl)methylidene]hydroxylamine Chemical compound O\N=C/C1=CC=CC=C1Cl FZIVKDWRLLMSEJ-UITAMQMPSA-N 0.000 claims description 4
- VTWKXBJHBHYJBI-VURMDHGXSA-N (nz)-n-benzylidenehydroxylamine Chemical compound O\N=C/C1=CC=CC=C1 VTWKXBJHBHYJBI-VURMDHGXSA-N 0.000 claims description 4
- DHEBWZWJJGNJNU-UHFFFAOYSA-N 5-(diethylamino)-2-(hydroxyiminomethyl)phenol Chemical compound C(C)N(C=1C=C(C(C=NO)=CC1)O)CC DHEBWZWJJGNJNU-UHFFFAOYSA-N 0.000 claims description 4
- 239000001632 sodium acetate Substances 0.000 claims description 4
- 235000017281 sodium acetate Nutrition 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 claims description 3
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 claims description 3
- ONJQBRVMFRQQIG-ONNFQVAWSA-N (ne)-n-[(2,4-dichlorophenyl)methylidene]hydroxylamine Chemical compound O\N=C\C1=CC=C(Cl)C=C1Cl ONJQBRVMFRQQIG-ONNFQVAWSA-N 0.000 claims description 2
- UJYKADYTQMVUAG-JXMROGBWSA-N (ne)-n-[[4-(dimethylamino)phenyl]methylidene]hydroxylamine Chemical compound CN(C)C1=CC=C(\C=N\O)C=C1 UJYKADYTQMVUAG-JXMROGBWSA-N 0.000 claims description 2
- IHMGDCCTWRRUDX-YVMONPNESA-N (nz)-n-[(2-nitrophenyl)methylidene]hydroxylamine Chemical compound O\N=C/C1=CC=CC=C1[N+]([O-])=O IHMGDCCTWRRUDX-YVMONPNESA-N 0.000 claims description 2
- DMIYKWPEFRFTPY-UHFFFAOYSA-N 2,6-dichlorobenzaldehyde Chemical compound ClC1=CC=CC(Cl)=C1C=O DMIYKWPEFRFTPY-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- JGUQDUKBUKFFRO-CIIODKQPSA-N dimethylglyoxime Chemical compound O/N=C(/C)\C(\C)=N\O JGUQDUKBUKFFRO-CIIODKQPSA-N 0.000 claims description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- ORIHZIZPTZTNCU-YVMONPNESA-N salicylaldoxime Chemical compound O\N=C/C1=CC=CC=C1O ORIHZIZPTZTNCU-YVMONPNESA-N 0.000 claims description 2
- ZFGMCJAXIZTVJA-XQRVVYSFSA-N (nz)-n-(2-methyl-2-methylsulfanylpropylidene)hydroxylamine Chemical compound CSC(C)(C)\C=N/O ZFGMCJAXIZTVJA-XQRVVYSFSA-N 0.000 claims 1
- ZKQNRRLCBJUEBC-UHFFFAOYSA-N oxo-[[1-[[4-(oxoazaniumylmethylidene)pyridin-1-yl]methyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CN1C=CC(=C[NH+]=O)C=C1 ZKQNRRLCBJUEBC-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 27
- 238000011065 in-situ storage Methods 0.000 abstract description 7
- 230000020169 heat generation Effects 0.000 abstract description 5
- 238000006146 oximation reaction Methods 0.000 abstract description 5
- 239000012736 aqueous medium Substances 0.000 abstract description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 75
- 239000000047 product Substances 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- 238000012565 NMR experiment Methods 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
- 230000003595 spectral effect Effects 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000012467 final product Substances 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 102000012440 Acetylcholinesterase Human genes 0.000 description 3
- 108010022752 Acetylcholinesterase Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229940022698 acetylcholinesterase Drugs 0.000 description 3
- 239000006184 cosolvent Substances 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- YBSXDWIAUZOFFV-UHFFFAOYSA-N n-[(2,6-dichlorophenyl)methylidene]hydroxylamine Chemical compound ON=CC1=C(Cl)C=CC=C1Cl YBSXDWIAUZOFFV-UHFFFAOYSA-N 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000000729 antidote Substances 0.000 description 2
- 229940075522 antidotes Drugs 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- QOWOXBFFQOXPHM-UHFFFAOYSA-O oxo-[[1-[[4-(oxoazaniumylmethylidene)pyridin-1-yl]methyl]pyridin-4-ylidene]methyl]azanium;chloride Chemical compound [Cl-].C1=CC(=C[NH+]=O)C=CN1CN1C=CC(=C[NH+]=O)C=C1 QOWOXBFFQOXPHM-UHFFFAOYSA-O 0.000 description 2
- JBKPUQTUERUYQE-UHFFFAOYSA-O pralidoxime Chemical compound C[N+]1=CC=CC=C1\C=N\O JBKPUQTUERUYQE-UHFFFAOYSA-O 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- AKSJAODDCCGRNN-UHFFFAOYSA-N C1=CC(=C(C(=C1)Cl)C=O)Cl.C1=CC(=CC=C1C=O)Cl Chemical compound C1=CC(=C(C(=C1)Cl)C=O)Cl.C1=CC(=CC=C1C=O)Cl AKSJAODDCCGRNN-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 229920002292 Nylon 6 Polymers 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- QELSIJXWEROXOE-UHFFFAOYSA-N asoxime chloride Chemical compound [Cl-].[Cl-].C1=CC(C(=O)N)=CC=[N+]1COC[N+]1=CC=CC=C1\C=N\O QELSIJXWEROXOE-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- FZIVKDWRLLMSEJ-UHFFFAOYSA-N n-[(2-chlorophenyl)methylidene]hydroxylamine Chemical compound ON=CC1=CC=CC=C1Cl FZIVKDWRLLMSEJ-UHFFFAOYSA-N 0.000 description 1
- MFSUKOCGNJOMDD-UHFFFAOYSA-N n-ethoxyacetamide Chemical compound CCONC(C)=O MFSUKOCGNJOMDD-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 229960004429 obidoxime Drugs 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- JHZHWVQTOXIXIV-UHFFFAOYSA-N oxo-[[1-[3-[4-(oxoazaniumylmethylidene)pyridin-1-yl]propyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCCN1C=CC(=C[NH+]=O)C=C1 JHZHWVQTOXIXIV-UHFFFAOYSA-N 0.000 description 1
- ZIFJVJZWVSPZLE-UHFFFAOYSA-N oxo-[[1-[[4-(oxoazaniumylmethylidene)pyridin-1-yl]methoxymethyl]pyridin-4-ylidene]methyl]azanium;dichloride Chemical compound [Cl-].[Cl-].C1=CC(=C[NH+]=O)C=CN1COCN1C=CC(=C[NH+]=O)C=C1 ZIFJVJZWVSPZLE-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229960003370 pralidoxime Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
- C07C249/08—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reaction of hydroxylamines with carbonyl compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/53—Nitrogen atoms
Definitions
- the present invention relates to an improved process for preparation of aldoxime of formula (I) with high purity and high yield.
- the present invention further relates to the process which is fast, simple, highly efficient, and reproducible.
- the oximes have large scale of application in the field of synthetic organic chemistry.
- An oxime is an intermediate in the industrial production of caprolactam, a precursor to Nylon 6.
- Oximes are commonly used as ligands and sequestering agents for metal ions.
- Oxime compounds are used as antidotes for nerve agents.
- a nerve agent inactivates acetylcholinesterase by phosphorylation.
- Oxime compounds can reactivate acetylcholinesterase by attaching to phosphorus, forming an oxime-phosphonate, which then splits away from the acetylcholinesterase molecule.
- Oxime nerve-agent antidotes are pralidoxime (also known as 2-PAM), obidoxime, methoxime, HI-6, Hl-7, and TMB-4.
- the effectiveness of the oxime treatment depends on the particular nerve agent used. Due to the nucleophilic character of oximes, they have been widely used for the preparation of a variety of nitrogen-containing compounds such as amides, hydroximinoyl chlorides, nitrones and nitriles. Oximation has attracted intensive attention for several decades as an efficient method for characterization and purification of carbonyl compounds. Oximes were usually prepared by the reaction of carbonyl compounds and hydroxylamine hydrochloride with adjustment of pH using a basic aqueous medium.
- W02008023248 discloses the process of preparing pyridine-2- carbaldehyde oxime from 2-pyridine carboxaldehyde and hydroxylamine hydrochloride using sodium acetate and methanol. The reaction takes place within 2 hours at 20-30°C.
- the reaction mixture was evaporated under vacuum to provide a crude mass.
- To the crude mass was stirred with water to effect precipitation and the separate solid was filtered under suction, dried under vacuum to provide pyridine-2-carbaldehyde oxime product in 85% yield.
- the Japanese patent application JP2016166153 discloses the catalytic transoximation reaction under mild conditions.
- the catalyst and water hydrolyzes the oxime compound ethyl acetohydroxamate, sequentially generates hydroxylamine, and reacts with the aldehyde to produce an aldoxime compound, which can be used under harsh reaction conditions without using expensive catalysts and reagents.
- a method for producing an aldoxime compound including a step of transoximing an aldehyde compound and an oxime compound in the presence of perchloric acid and / or a perchloric acid metal salt in an organic solvent and water.
- reaction temperature is not specifically limited, 10-40°C is preferable and 20- 30°C is more preferable. Above 40°C, the solvent tends to volatilize.
- reaction time is not specifically limited, 12 to 72 hours are preferable and 24 to 72 hours are more preferable. If it is less than 12 hours, the reaction tends to be incomplete.
- the inventors of the present invention therefore, have come up with an improved process for preparing the aldoxime wherein the said process is simple, with minimum processing steps, provides high yield with maximum purity and without the usage of any organic solvents and/or limited use of co-solvent.
- the present invention discloses the process of oximation of aldehydes to obtain aldoxime.
- the present invention eliminates the usage of external heat and long reaction time, by implementing the concept of in-situ heat generation.
- the in-situ heat generation takes place in presence of strong or weak base and increases the temperature of reaction mixture to more than 70°C and accelerates the process.
- the product thus obtained is pure, with high yield and obtained in very less time as low as less than 3 hours in comparison with overnight process as disclosed in the prior art.
- the present invention minimises the usage of organic solvents and additional co-solvents, there are less impurities in final product.
- the present process eliminates the lengthy and expensive processing steps of purification of final yield.
- the main object of the present invention is to provide an improved process for the preparation of aldoximes of formula (I), wherein the said process is simple, economical, user- friendly and commercially viable.
- Another objective of the present invention is to provide a process for the preparation of aldoxime of formula (I), wherein the process is carried out at room temperature and without any additional organic solvents and/or with limited use of cosolvents.
- Yet another objective of the present invention is to provide a process for the preparation of an aldoxime of formula (I) with a high yield and high chemical purity.
- Yet another objective of the present invention is to provide a process for the preparation of an aldoxime of formula (I) with a yield of the final product is more than 90 percent.
- Present invention provides a simple, highly efficient, economical, industrially viable and reproducible process for preparation of aldoximes provide high yield of pure aldoxime.
- the present invention provides an improved process for preparation of aldoxime wherein the said process is carried out at room temperature and without additional organic solvents and/or with limited use of cosolvents.
- the present invention provides the process for preparing aldoxime using inexpensive raw materials merely in aqueous media and generation of in situ heat that expedites the rate of reaction and provides the final product within as less as 3 hours.
- the present invention provides the process for preparing aldoxime, wherein the said process does not involve use of any catalyst or any aqueous work up, does not require any complex purification process such as column chromatography or recrystallization method, does not require any drying agents such as Na 2 SC> 4 , MgCCb, or CaCb and the like in order to dehydrate product and make product moisture free, does not need product concentration with complex process such as downword distillation or under reduced pressure/vacuum distillation.
- the present invention provides an improved process for the preparation of aldoxime of formula (I), which is synthesized in the higher yield under oximation reaction of aldehyde with hydroxylamine hydrochloride merely in aqueous medium using of in situ heat generation.
- R H, alkyl, alkyl halide, heterocyclic aromatic ring, substituted or unsubstituted heterocyclic aromatic ring, halide group, mono-, di-, tri-substituted aromatic group, macrocyclic groups including but not limiting to porphyrins and dendrimers.
- the present invention an improved process for the preparation of pyridine-2-aldoxime of formula (II), wherein the said process comprises the steps of: i) preparing a solution of hydroxylamine hydrochloride and water; ii) adding water soluble strong or weak base in the reaction mixture of step (i); iii) adding 2-pyridine aldehyde in above solution; iv) stirring the mixture of step (iii) for less than 3 hours; a pure pyridine-2-aldoxime thus obtained is separated from the reaction mixture, wherein the sequence of the above processing steps can be interchangeable in any possible order.
- the present invention an improved process for the preparation of pyridine-3-aldoxime of formula (IV), wherein the said process comprises the steps of: i) preparing a solution of hydroxylamine hydrochloride and water; ii) adding 3 -pyridine aldehyde in above solution; iii) adding water soluble strong or weak base in the reaction mixture of step (ii); iv) stirring the mixture of step (iii) for less than 3 hours; a pure pyridine-3 -aldoxime thus obtained is separated from the reaction mixture, wherein the sequence of the above processing steps can be interchangeable in any possible order.
- the present invention discloses an improved process for preparing aldoximes.
- the present invention provides the improved process for preparing aldoxime.
- the present invention provides the improved process for preparing aldoxime from aldehyde, wherein the said process is carried out in presence of water and water-soluble base.
- the present invention provides the improved process for preparing an aldoxime, wherein the water-soluble base is selected from but not limiting to the strong or weak bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate and the like.
- the strong or weak bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate and the like.
- the present invention provides the improved process for preparing aldoxime from aldehyde, wherein the said aldehyde undergoes oximation reaction in presence of hydroxylamine hydrochloride and water with strong or weak water-soluble base to obtain the pure aldoxime.
- the present invention provides the improved process for preparing aldoxime, wherein the aldoxime thus obtained is in the polymorphic crystalline form or amorphous form. In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the aldoxime thus obtained is highly pure and crystalline in nature.
- the present invention provides the improved process for preparing aldoxime, wherein the aldoxime thus obtained in the form of E isomer or Z isomer or both.
- the present invention provides the improved process for preparing aldoxime, wherein the aldoxime thus prepared is selected from group consisting of but not limiting to 2-pyridine aldoxime, 3-pyridine aldoxime, 2-chloro benzaldehyde oxime, anisaldehyde oxime, salicaldehyde oxime, dimethylglyoxime, 2- thiophene aldehyde oxime, 4-chlorobenzaldehyde oxime, 2, 4-dichlorobenzaldehyde oxime, 2, 6-dichlorobenzaldehyde oxime, 2-Nitro benzaldehyde oxime, 4- (dimethylamino) benzaldehyde oxime, 2-hydroxybenzaldehyde oxime, ketoxime, methoxi
- R H, alkyl, alkyl halide, heterocyclic aromatic ring, substituted or unsubstituted heterocyclic aromatic ring, halide group, mono-, di-,tri-substituted aromatic group, macrocyclic groups including but not limiting to porphyrins and dendrimers.
- the present invention provides the improved process for preparing aldoxime, wherein the aldehyde used for preparing aldoxime is selected from group consisting of but not limiting to 2-pyridine aldehyde, 3 -pyridine aldehyde, 2- chloro benzaldehyde, anisaldehyde, salicaldehyde, 2-thiophene aldehyde, 2-chloro benzaldehyde, 4-chloro benzaldehyde 2,6-dichlorobenzaldehyde, 4- methoxybenzaldehyde, 2,3-dimethoxy benzaldehyde, 4-tolualdehyde, 3-pyridyl carbaldehyde, 4-pyridyl carbaldehyde, 2-salisaldehyde, 2,3-dimethoxy benzaldehyde, 2- hydroxy 4-diethylamine benzaldehyde, benzaldehyde and the like.
- the present invention provides the improved process for preparing aldoxime, wherein the said process is carried out at temperature below 50°C. In yet another embodiment the present invention provides the improved process for preparing aldoxime, wherein the said process implements the concept of in-situ heat generation and does not require any external heating for reaction to take place. In yet another embodiment the present invention provides the improved process for preparing aldoxime, wherein the yield of aldoxime thus obtained is more than 90% of crude aldoxime.
- the present invention provides the improved process for preparing aldoxime, wherein said pure aldoxime is in the form of powder or crystalline or crystalline powdered form.
- the present invention provides the improved process for preparing aldoxime, wherein the said process takes place within the pH range of 8-12, more specifically, within the pH range of 9-11. In yet another embodiment, the present invention provides the improved process for preparing aldoxime, wherein the said process eliminates the lengthy and expensive conventional steps for purification of final product.
- the said process comprises the steps of: i) preparing a solution of hydroxylamine hydrochloride and water; ii) adding water soluble strong or weak base in the reaction mixture of step (i); iii) adding suitable aldehyde in above solution; iv) stirring the mixture of step (iii) for less than 3 hours; v) a pure aldoxime thus obtained is separated from the reaction mixture, wherein the sequence of the above processing steps can be interchangeable in any possible order.
- the present invention provides an improved process for the preparation of pyridine- 2-aldoxime of formula (II), wherein the said process comprises the steps of: i) preparing a solution of hydroxylaminehydrochloride and water; ii) adding water soluble strong or weak base in the reaction mixture of step (i); iii) adding 2-pyridine aldehyde in above solution; iv) stirring the mixture of step (iii) for less than 3 hours; v) a pure pyridine-2-aldoxime thus obtained is separated from the reaction mixture.
- the sequence of the above processing steps can be interchangeable in any possible order.
- the said process comprises the steps of: i) preparing a solution of hydroxylamine hydrochloride and water; ii) adding suitable aldehyde in above solution; iii)adding water soluble strong or weak base in the reaction mixture of step (ii); iv) stirring the mixture of step (iii) for less than 3 hours; v) a pure aldoxime thus obtained is separated from the reaction mixture, wherein the sequence of the above processing steps can be interchangeable in any possible order.
- the present invention provides an improved process for the preparation of aldoxime, wherein the sequence of processing steps can be interchangeable in any possible order.
- one step or all step may be performed in in-situ manner.
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.
- a strong or weak base selected from group but not limiting to NaHCCb, Na 2 CC> 3 , NaOH, NaOAc, KOH
- 3 -pyridine aldehyde was slowly added 3 -pyridine aldehyde by keeping temperature below 83°C.
- crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 3- pyridine aldoxime of formula IV.
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.
- a strong or weak base selected from group but not limiting to NaHCCb, NaiCCL, NaOH, NaOAc, KOH
- 3-pyridine aldehyde was slowly added in order to keep temperature below 41 °C and PH of the solution 6.6.
- 3-pyridine aldehyde was kept temperature below 59°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 3 -pyridine oxime.
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.
- a strong or weak base selected from group but not limiting to NaHCCb, NaiCCL, NaOH, NaOAc, KOH
- 2-Chloro benzaldehyde was added in order to keep the temperature below 50°C and pH of the solution below 9.5.
- 2-Chloro benzaldehyde was slowly added to keep temperature below 83°C.
- crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2-Chloro benzaldehyde by keeping temperature below 83°C.
- Example no. 4 A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution 2-Chloro benzaldehyde was added in order to keep temperature below 20°C. To this solution NaOH was added till product precipitation was observed by keeping temperature below 74°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2-Chloro benzaldehyde oxime.
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.
- NaOH was added in order to keep the temperature below 50°C and pH of the solution below 9.5.
- 4-Chlorobenzaldehyde was slowly added by keeping temperature below 83°C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of 35% aq. Methanol in order to keep the pH of solution below 2.6 and temperature below 25°C.
- KOH in order to keep temperature below 41 °C and pH of the solution 6.6.
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of 35% aq. Methanol in order to keep the pH of solution below 2.6 and temperature below 25°C.
- KOH in order to keep temperature below 41 °C and pH of the solution 6.6.
- 2-pyridine aldehyde 23 mM
- Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 2-pyridine aldoxime.
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.
- a strong or weak base selected from group but not limiting to NaHCC , NaiCC , NaOH, NaOAc, KOH
- 2-pyridine aldehyde (0.23M) by keeping temperature below 83°C.
- TLC Reaction liquid phase
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.
- NaOH was added in order to keep the temperature below 50°C and pH of the solution below 9.5.
- To this warm solution was slowly added 2,6-dichlorobenzaldehyde by keeping temperature below 83°C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2,6-dichlorobenzaldehyde oxime of formula VIII.
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution KOH was added in order to keep temperature below 41 °C and pH of the solution 6.6. To this solution was slowly added 2-thiophene aldehyde by keeping temperature below 59°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 2-thiophene aldehyde oxime of formula IX.
- Example no. 16 A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution 2-pyridine aldehyde (93.3 mM) was added in order to keep temperature below 20°C. To this solution sodium carbonate was added till product precipitation was observed by keeping temperature below 74°C.
- Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2-pyridine oxime.
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution sodium acetate was added in order to keep temperature below 41 °C and pH of the solution 6.6. To this solution was slowly added 2-pyridine aldehyde (23 mM) by keeping temperature below 59°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered 2-pyridine oxime.
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.
- sodium bicarbonate was added in order to keep the temperature below 50°C and pH of the solution below 9.5.
- To this warm solution was slowly 2-hydroxy 4-diethylamine benzaldehyde by keeping temperature below 83 °C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC.
- Example no. 20 A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution 4-Chlorobenzaldehyde was added in order to keep temperature below 20°C. To this solution sodium carbonate was added till product precipitation was observed by keeping temperature below 74°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours.
- a solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25°C.To this solution KOH was added in order to keep temperature below 41 °C and pH of the solution 6.6. To this solution was slowly added benzaldehyde by keeping temperature below 59°C. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain powdered benzaldehyde oxime of formula XII.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN201921051588 | 2019-12-12 | ||
IN201921051588 | 2019-12-12 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2021117053A1 true WO2021117053A1 (en) | 2021-06-17 |
Family
ID=76329708
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IN2020/050704 WO2021117053A1 (en) | 2019-12-12 | 2020-08-12 | An improved process for preparation of pure aldoxime |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2021117053A1 (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4323706A (en) * | 1978-02-23 | 1982-04-06 | Allied Corporation | Production of acetaldehyde oxime |
US4922017A (en) * | 1988-06-20 | 1990-05-01 | Allied-Signal Inc. | Process for production of aromatic aldoximes |
-
2020
- 2020-08-12 WO PCT/IN2020/050704 patent/WO2021117053A1/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4323706A (en) * | 1978-02-23 | 1982-04-06 | Allied Corporation | Production of acetaldehyde oxime |
US4922017A (en) * | 1988-06-20 | 1990-05-01 | Allied-Signal Inc. | Process for production of aromatic aldoximes |
Non-Patent Citations (1)
Title |
---|
DAMLIJANOVIC I ET AL.: "A Simple Synthesis of Oximes", MONATSH CHEM., vol. 137, 2 February 2006 (2006-02-02), pages 301 - 305, XP019378883, DOI: 10.1007/s00706-005-0427-3 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Veisi et al. | Chemoselective hydration of nitriles to amides using hydrated ionic liquid (IL) tetrabutylammonium hydroxide (TBAH) as a green catalyst | |
JP5249219B2 (en) | Process for the preparation of 2-substituted-5- (1-alkylthio) alkylpyridines | |
Yi et al. | Mannich-type reactions of aromatic aldehydes, anilines, and methyl ketones in fluorous biphase systems created by rare earth (III) perfluorooctane sulfonates catalysts in fluorous media | |
CN104529786B (en) | The synthetic method of the fluoro- 2 '-nitrobiphenyl of 3,4,5- tri- | |
JP6811717B2 (en) | Methods for the preparation of topiroxostat and its intermediates | |
JP5916721B2 (en) | Synthetic method of ferroquine by intensive reductive amination | |
JP5256029B2 (en) | Method for producing 3,7-diaza-bicyclo [3.3.1] nonane compound | |
JP6073223B2 (en) | Process for producing optically active tetrahydroquinolines | |
CN107602570B (en) | Method for synthesizing nitrogen-containing multi-membered heterocyclic compound | |
WO2021117053A1 (en) | An improved process for preparation of pure aldoxime | |
CN104220417A (en) | Method for synthesising aminobiphenyls using aryl hydrazines | |
JP7454498B2 (en) | Method for producing salicylamide acetate | |
JP6228210B2 (en) | Method for purifying fluvoxamine free base and method for producing high purity fluvoxamine maleate using the same | |
JPWO2005070864A1 (en) | Enantioselective nucleophilic addition reaction to enamide carbonyl group and synthesis method of optically active α-hydroxy-γ-keto acid ester and hydroxy diketone | |
CN105017147B (en) | A method of recycling and utilize Bedaquiline three-dimensional chemical isomer | |
JP6251197B2 (en) | Process for preparing substituted phenylpropanones | |
CN111892627B (en) | Method for synthesizing alpha-amino phosphorus oxide | |
CN108586427B (en) | Preparation method of atorvastatin calcium intermediate | |
CN111909057B (en) | Preparation method of cyclopentenyl aryl ketoxime compound | |
CN108299224A (en) | A kind of preparation method of N- acetyl group -1- cyclohexylethylamines | |
CN110818588A (en) | Preparation method of pyrazole amide bactericide intermediate ketene oxime compound | |
KR100841407B1 (en) | Allenyn-1,6-diol derivatives, and process for preparing them | |
CN110407902B (en) | Method for removing 17-acetoxyl group from steroid compound | |
JP6038800B2 (en) | Method for producing optically active alcohol | |
JP4538993B2 (en) | Process for producing β-ketonitrile derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 20898867 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 20898867 Country of ref document: EP Kind code of ref document: A1 |
|
32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 29/03/2023) |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 20898867 Country of ref document: EP Kind code of ref document: A1 |