JP2017523962A - 4−アルコキシ−3−ヒドロキシピコリン酸の製造方法 - Google Patents
4−アルコキシ−3−ヒドロキシピコリン酸の製造方法 Download PDFInfo
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- JP2017523962A JP2017523962A JP2017500360A JP2017500360A JP2017523962A JP 2017523962 A JP2017523962 A JP 2017523962A JP 2017500360 A JP2017500360 A JP 2017500360A JP 2017500360 A JP2017500360 A JP 2017500360A JP 2017523962 A JP2017523962 A JP 2017523962A
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- 238000000034 method Methods 0.000 title claims description 71
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 claims abstract description 25
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- 229910052794 bromium Inorganic materials 0.000 claims abstract description 18
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- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102100026459 POU domain, class 3, transcription factor 2 Human genes 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 239000004280 Sodium formate Substances 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000005219 aminonitrile group Chemical group 0.000 description 1
- SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 239000012431 aqueous reaction media Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- BUTPBERGMJVRBM-UHFFFAOYSA-N methanol;methylsulfinylmethane Chemical compound OC.CS(C)=O BUTPBERGMJVRBM-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229940081066 picolinic acid Drugs 0.000 description 1
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000010963 scalable process Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- XGGKIQWPUMUBNO-UHFFFAOYSA-M sodium 6-bromo-2-cyano-4-methoxypyridin-3-olate Chemical compound BrC1=CC(=C(C(=N1)C#N)[O-])OC.[Na+] XGGKIQWPUMUBNO-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 108010072897 transcription factor Brn-2 Proteins 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
-
- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Pharmacology & Pharmacy (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
Description
本出願は、2014年7月8日に出願された米国仮特許出願第62/021,876号、2014年7月8日に出願された米国仮特許出願第62/021,877号、および2014年7月8日に出願された米国仮特許出願第62/021,881号の利益を主張し、それぞれが参照によって本明細書に個々に組み込まれるように、そのそれぞれはその全体が参照によって本明細書に明示的に組み込まれる。
本開示は、4−アルコキシ−3−ヒドロキシピコリン酸の製造方法に関する。より詳細には、本開示は、フルフラールからの4−アルコキシ−3−ヒドロキシピコリン酸の製造方法に関する。
米国特許第6,521,622号明細書、ならびに米国特許出願公開第61/747,723号明細書および第14/142,183号明細書には、とりわけ、特定の一般式
本発明の態様の第1のセットは、式A:
MOR1 E
[式中、MはNaまたはKであり、R1はC1〜C3アルキルである]のアルカリ金属アルコキシド、および式Aの化合物を含有する第6の混合物を作製するステップ、b)混合物を加熱するステップ、ならびにc)第6の混合物から、式F
a)式F
MOR1 E
[式中、MはNaまたはKであり、R1はC1〜C3アルキルである]のアルカリ金属アルコキシド、および式A
MOR1 E
[式中、MはNaまたはKであり、R1はC1〜C3アルキルである]のアルカリ金属アルコキシド、および式Aの化合物を含有する第1の混合物を作製するステップ、b)混合物を加熱するステップ、ならびにc)第1の混合物から、式F
MOR1 E
[式中、MはNaまたはKであり、R1はC1〜C3アルキルである]のアルカリ金属アルコキシド、および式Aの化合物を含有する混合物を作製するステップ、ならびにb)混合物から、式F
本明細書で使用される用語「単離する」、「単離すること」または「単離」は、限定するものではないが、ろ過、抽出、蒸留、結晶化、遠心分離、粉砕、液−液相分離または他の当業者に公知の方法等の標準的な方法を使用して、終了した化学的プロセスの混合物の他の成分から、所望の生成物を部分的または完全に取り出すことを意味する。単離した生成物は、≦50%〜≧50%の範囲の純度を有していてよく、標準的な精製方法を使用して、より高純度に精製してよい。単離した生成物は、精製して、または精製することなく、次のプロセスのステップで使用してもよい。
本明細書に記載の方法において、化学的ステップa、bおよびcを、スキームIに表すようにして行い、ジブロモヒドロキシピコリノニトリルAを製造する。
式Hの4−アルコキシ−3−ヒドロキシピコリン酸を製造するために、化学的ステップd、eおよびfは、スキームIIに表すように2つの異なる順序で行ってよい。式Aの化合物の4−ブロモ基をアルコキシ基に置き換えるための置換反応において(ステップd)、式MOR1(Mはアルカリ金属であり、R1はC1〜C3アルキルである)のアルカリ金属アルコキシドを使用して、式Fの4−アルコキシ−6−ブロモ−3−ヒドロキシピコリノニトリルを製造する。少なくとも2当量、好ましくは2〜5当量のアルカリ金属アルコキシドを当該反応で使用する。当該反応で有用な典型的なアルカリ金属アルコキシドとしては、ナトリウムまたはカリウムの、メトキシド、エトキシド、1−プロポキシドまたは2−プロポキシドが挙げられる。
Claims (32)
- 式A
a)2相の水−有機溶媒系、アンモニア源、シアニド源および式B
b)前記第1の混合物から、前記有機溶媒中の溶液として式C
c)鉱酸の水溶液を前記第2の混合物に添加して、第3の混合物を形成するステップ、
d)式D
の化合物を含有する水性混合物である前記第3の混合物から、第4の混合物を分離するステップ、
e)臭素化剤を前記第4の混合物に添加して、第5の混合物を形成するステップ、ならびに
f)前記第5の混合物から、式Aの化合物を単離するステップ
を含む、方法。 - 前記有機溶媒が、ジエチルエーテル、メチルt−ブチルエーテル、塩化メチレン、酢酸エチル、2−メチルテトラヒドロフラン、トルエンおよびキシレンからなる有機溶媒の群から選択される少なくとも1種の有機溶媒である、請求項1に記載の方法。
- 前記鉱酸が臭化水素酸である、請求項1に記載の方法。
- XがBrである、請求項1に記載の方法。
- 前記臭素化剤が臭素である、請求項1に記載の方法。
- ステップ:
a)式E
MOR1 E
[式中、MはNaまたはKであり、R1はC1〜C3アルキルである]のアルカリ金属アルコキシド、および式Aの化合物を含有する第6の混合物を作製するステップ、
b)前記混合物を加熱するステップ、ならびに
c)前記第6の混合物から、式F
をさらに含む、請求項1に記載の方法。 - ステップ:
a)式Fの化合物、水、ならびに鉱酸および強塩基の少なくとも1種を含有する第7の混合物を作製するステップ、
b)前記混合物を加熱するステップ、ならびに
c)前記第7の混合物から、式G
をさらに含む、請求項6に記載の方法。 - 前記第7の混合物が式Fの化合物、水および鉱酸を含有する、請求項7に記載の方法。
- 前記鉱酸が硫酸である、請求項8に記載の方法。
- 前記第7の混合物が式Fの化合物、水および強塩基を含有する、請求項7に記載の方法。
- 前記強塩基が、水酸化ナトリウムおよび水酸化カリウムからなる群から選択される少なくとも1種の強塩基である、請求項10に記載の方法。
- 以下のステップ:
a)式Gの化合物、および還元剤を含有する第8の混合物を作製するステップ、ならびに
b)前記第8の混合物から、式H
をさらに含む、請求項7に記載の方法。 - 前記還元剤が水素および遷移金属触媒から構成される、請求項12に記載の方法。
- 前記水素が水素ガスであり、前記遷移金属触媒がパラジウム炭素から構成される、請求項13に記載の方法。
- 前記還元剤が亜鉛金属から構成される、請求項12に記載の方法。
- 以下のステップ:
a)式Fの化合物、および還元剤を含有する第9の混合物を作製するステップ、ならびに
b)前記第9の混合物から、式I
をさらに含む、請求項6に記載の方法。 - 前記還元剤が水素および遷移金属触媒から構成される、請求項16に記載の方法。
- 前記還元剤が亜鉛金属から構成される、請求項16に記載の方法。
- ステップ:
a)式Iの化合物、水、ならびに鉱酸および強塩基の1種を含有する第10の混合物を作製するステップ、ならびに
b)前記第10の混合物から、式H
をさらに含む、請求項16に記載の方法。 - ステップ:
前記第10の混合物を加熱するステップ、
をさらに含む、請求項19に記載の方法。 - 前記第10の混合物が式Iの化合物、水および鉱酸を含有する、請求項19に記載の方法。
- 前記鉱酸が硫酸である、請求項21に記載の方法。
- 前記第10の混合物が式Iの化合物、水および強塩基を含有する、請求項19に記載の方法。
- 前記強塩基が、水酸化ナトリウムおよび水酸化カリウムからなる群から選択される少なくとも1種の強塩基である、請求項23に記載の方法。
- 式H
a)式F
b)前記混合物を加熱するステップ、ならびに
c)前記混合物から、式Hの化合物を単離するステップ
を含む、方法。 - 前記強塩基が水酸化カリウムである、請求項25に記載の方法。
- 式F
a)少なくとも1種の式E
MOR1 E
[式中、MはNaまたはKであり、R1はC1〜C3アルキルである]のアルカリ金属アルコキシド、および式A
b)前記混合物を加熱するステップ、ならびに
c)前記混合物から、式Fの化合物を単離するステップ
を含む、方法。 - MがNaであり、R1がC1〜C3アルキルである、請求項27に記載の方法。
- プロトン性溶媒および極性の非プロトン性溶媒から構成される溶媒混合物をさらに含む、請求項27に記載の方法。
- 前記プロトン性溶媒が、メタノールおよびエタノールからなる群から選択される少なくとも1種の溶媒である、請求項29に記載の方法。
- 前記非プロトン性溶媒が、DMSO、DMF、スルホラン、およびNMPからなる群から選択される少なくとも1種の溶媒である、請求項29に記載の方法。
- 前記溶媒混合物における前記プロトン性溶媒と前記極性の非プロトン性溶媒の容積パーセントの比率が約100:0〜約0:100である、請求項29に記載の方法。
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