EP1070039A1 - Procede d'oxydation au moyen de tempo - Google Patents

Procede d'oxydation au moyen de tempo

Info

Publication number
EP1070039A1
EP1070039A1 EP99916376A EP99916376A EP1070039A1 EP 1070039 A1 EP1070039 A1 EP 1070039A1 EP 99916376 A EP99916376 A EP 99916376A EP 99916376 A EP99916376 A EP 99916376A EP 1070039 A1 EP1070039 A1 EP 1070039A1
Authority
EP
European Patent Office
Prior art keywords
recited
substituted
unsubstituted
cycloalkyl
alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP99916376A
Other languages
German (de)
English (en)
Inventor
Jing Li
David M. Tschaen
Zhiguo Song
Mangzu Zhao
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB9810188.4A external-priority patent/GB9810188D0/en
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Publication of EP1070039A1 publication Critical patent/EP1070039A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/02—Formation of carboxyl groups in compounds containing amino groups, e.g. by oxidation of amino alcohols
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
    • C07C51/29—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with halogen-containing compounds which may be formed in situ
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring

Definitions

  • Oxidation is one of the most fundamental transformations in organic synthesis and there are numerous methods reported in the literature. (Hudlicky, M. "Oxidations In Organic Chemistry", ACS Monograph No. 186 American Chemical Society Washington D.C. (1990).) However, relatively few methods exist for the oxidation of primary alcohols to the corresponding carboxylic acids. The most commonly used ones are CrO 3 /H 2 SO 4 (Bowden; Heilbron; Jones; Weedon J. Chem. Soc, 1946, 39; Bowers; H.; Jones; L. J. Chem. Soc, 1953, 2548; Millar, J. G.; Oehlschlager, A. C; Wong, J. W. J. Org.
  • the present invention relates to an oxidation using sodium chlorite in the presence of a catalytic amount of TEMPO and sodium hypochlorite which converts a primary alcohol to a carboxylic acid.
  • This oxidation method avoids the disposal issues associated with running a Jones oxidation (CrO 3 /H 2 SO 4 ) reaction, as well as reducing the epimerization of any ⁇ -chiral centers and is a one step procedure.
  • the present invention reduces this problem.
  • the present invention discloses a process for preparing a compound of Formula I:
  • R! is ! a) H, b) Ci-Cs alkyl, c) C2-C8 alkynyl, d) C3-C7 cycloalkyl, e) aryl, ) heteroaryl, or g) heterocyclyl;
  • Ci-Cs alkyl, C2-C8 alkynyl, or C3-C8 cycloalkyl are unsubstituted or substituted with one, two or three substituents selected from the group consisting of: OH,
  • CO2R 4 Br, Cl, F, I, CF3, Ci-Cs alkoxy, C3-C8 cycloalkyl, aryl, heteroaryl, heterocyclyl, and CO(CH2)nCH3,
  • aryl is defined as phenyl or naphthyl , which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: OH, CO2R 4 , Br, Cl, F, I, CF3, Ci-Cs alkoxy, Ci-Cs alkyl, C2-C8 alkynyl, or C3-C8 cycloalkyl, CO(CH2)nCH3, or when aryl is substituted on adjacent carbons they can form a 5- or 6-membered fused ring having one, two or three heteroatoms selected from O, N, and S, this ring is unsubstituted or substituted on carbon or nitrogen with one, two or three substituents selected from the group consisting of: OH, CO2R 4 , Br, Cl, F, I, CF3, Ci-Cs alkoxy, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cyclo
  • heteroaryl is defined as a 5- or 6-membered aromatic ring containing 1, 2 or 3 heteroatoms selected from O, N and S , which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: OH, CO2R 4 , Br, Cl, F, I, CF3, Ci-Cs alkoxy, Ci-Cs alkyl, C2-C8 alkynyl, C3-C8 cycloalkyl, CO(CH2) n CH3, and additionally the 5- or 6-membered aromatic ring can be benzofused and unsubstituted or substituted with one, two or three substituents as described above;
  • heterocyclyl is defined as a 5- or 6-membered, non-aromatic ring containing 1, 2 or 3 heteroatoms selected from O, N and S , which may contain one or two double bonds and which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: OH, CO2R 4 , Br, Cl, F, I, CF3, Ci-Cs alkoxy, Ci-Cs alkyl, C2-C8 alkynyl, or C3-C8 cycloalkyl, CO(CH2) n CH3, and additionally the 5- or 6-membered ring can be benzofused and unsubstituted or substituted with one, two or three substituents as described above;
  • n 0 to 5;
  • t 0, 1 or 2;
  • R 4 is: H, or Ci-Cs alkyl
  • Rl is a) H, b) Ci-Cs alkyl, c) C2-C8 alkynyl, d) C3-C7 cycloalkyl, e) aryl, f) heteroaryl, or g) heterocyclyl;
  • Ci-Cs alkyl, C2-C8 alkynyl, or C3-C8 cycloalkyl are unsubstituted or substituted with one, two or three substituents selected from the group consisting of: OH, CO2R 4 , Br, Cl, F, I, CF3, Ci-Cs alkoxy, C3-C8 cycloalkyl, aryl, heteroaryl, heterocyclyl, and CO(CH2)nCH3,
  • aryl is defined as phenyl or naphthyl , which is unsubstituted or - substituted with one, two or three substituents selected from the group consisting of: OH, CO2R 4 , Br, Cl, F, I, CF3, Ci-Cs alkoxy, Ci-Cs alkyl, C2-C8 alkynyl, or C3-C8 cycloalkyl, CO(CH2)nCH3, or when aryl is substituted on adjacent carbons they can form a 5- or 6-membered fused ring having one, two or three heteroatoms selected from O, N, and S, this ring is unsubstituted or substituted on carbon or nitrogen with one, two or three substituents selected from the group consisting of: OH, CO2R 4 , Br, Cl, F, I, CF3, Ci-Cs alkoxy, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8
  • heteroaryl is defined as a 5- or 6-membered aromatic ring containing 1, 2 or 3 heteroatoms selected from O, N and S , which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: OH, CO2R 4 , Br, Cl, F, I, CF3, C1-C8 alkoxy, Ci-Cs alkyl, C2-C8 alkynyl, C3-C8 cycloalkyl, CO(CH2) n CH3, and additionally the 5- or 6-membered aromatic ring can be benzofused and unsubstituted or substituted with one, two or three substituents as described above;
  • heterocyclyl is defined as a 5- or 6-membered, non-aromatic ring containing 1, 2 or 3 heteroatoms selected from O, N and S , which may contain one or two double bonds and which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: OH, CO2R 4 , Br, Cl, F, I, CF3, C1-C8 alkoxy, Ci-Cs alkyl, C2-C8 alkynyl, C3-C8 cycloalkyl, CO(CH2) n CH3, and additionally the 5- or 6-membered ring can be benzofused and unsubstituted or substituted with one, two or three substituents as described above;
  • n 0 to 5;
  • t 0, 1 or 2;
  • R 4 is: H, or Ci-Cs alkyl
  • the solvent is selected from the group consisting of: acetonitrile, tetrahydrofuran, acetone, tertiary C 4 -C 8 -alcohol, diethyl ether, DME (dimethyl ether), diglyme, triglyme, MTBE (methyl t-butyl ether), toluene, benzene, hexane, pentane, dioxane, dichloromethane, chloroform, carbon tetrachloride, or a mixture of said solvents.
  • the solvent is selected from the group consisting of: acetonitrile, tetrahydrofuran, acetone, tertiary C 4 -C 8 -alcohol, diethyl ether, DME (dimethyl ether), diglyme, triglyme, MTBE (methyl t-butyl ether), toluene, benzene, hexane, pentan
  • the phosphate buffer comprises an aqueous mixture of NaOH, KOH, NaH 2 PO 4 , KH 2 PO 4 , Na 2 HPO 4 , and j HPO ⁇ sufficient to maintain a pH of about 4.0 to about 8.0, and preferably a pH of about 6.5 to about 7.0.
  • TEMPO 2,2,6,6- tetramethyl-1-piperidinyloxy, free radical
  • reaction temperature is about 0°C to about 50°C, and preferably about 35°C to about 40°C.
  • reaction time is up to about 24 hours, and preferably between about 2 and about 4 hours.
  • alkyl substituents recited above denote straight and branched chain hydrocarbons of the length specified such as methyl, ethyl, isopropyl, isobutyl, tert-butyl, neopentyl, isopentyl, etc.
  • Cycloalkyl denotes rings composed of 3 to 8 methylene groups, each of which may be substituted or unsubstituted with other hydrocarbon substituents, and include for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and 4-methylcyclohexyl.
  • the alkoxy substituent represents an alkyl group as described above attached through an oxygen bridge.
  • the aryl substituent represents phenyl and 1-naphthyl or 2- naphthyl, including aryls substituted with a 5- or 6-membered fused ring, such as an unsubstituted and substituted methylenedioxy, oxazolyl, imidazolyl, or thiazolyl ring.
  • the heteroaryl substituent represents a carbazolyl, furanyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrazolyl, pyrazinyl, pyridyl, pyrimidyl, purinyl.
  • the heterocyclyl substituent represents, oxazolidinyl, thiazolidinyl, thiazolidinyl, oxadiazolyl, or thiadiazolyl.
  • Each of the above substituents can be either — unsubstituted or substituted as defined within the description.
  • the reaction was then optimized regard to further reduce the chlorination and enhance the safety for scale up.
  • the reaction was faster at lower pH, but it was accompanied by increased chlorination. It was slower at lower temperature as expected, but surprisingly, the chlorination level appeared to be slightly elevated.
  • Increasing the amount of TEMPO and bleach increased the reaction rate, but the TEMPO NaClO ratio should be >2 to reduce the chances of chlorination.
  • the bleach was added slowly and simultaneously with NaClO 2 to the batch at 35 °C to prevent build up of the oxidant and the risk of a run away reaction. It should be noted that mixing of bleach and NaClO 2 prior to the addition is not advised since some toxic and potentially explosive chlorine dioxide (ClO 2 ) may be generated.
  • reaction mixture is cooled to 15°C and carefully quenched into a cold (10 °C) saturated ammonium chloride solution (150 mL) while maintaining the temperature ⁇ 25°C.
  • Ethyl acetate (500 mL) is added and the layers are separated. The organic layer is washed with water (100 mL) and then transfered to a 1L round bottom flask equipped for distillation. The solution was concentrated and charged with fresh ethyl acetate. This is repeated until a solution with a volume of 200 mL has KF ⁇ 200 ⁇ g/mL. The solvent is then switched to DMF to give the final volume of 200 mL with a KF ⁇ 200 ⁇ g/mL.
  • the addition funnel is charged with water (400 mL) which is added dropwise to the reaction mixture over a period of 30 min. while maintaining the temperture ⁇ 15°C.
  • the temperature is controlled by 16
  • the benzyl chloride is isolated by filtration. The cake is washed with (1:1) DMF:H 2 O (lOOmL) and then water (200 mL). The solid is dried in vacuo to give 93 g of the benzyl chloride( 94% yield, 96 A%).
  • Methoxypropene (140 mL) is charged to an addition funnel and added over 30 minutes at a temperature of 50°C.
  • reaction slurry is aged for 1-2 hours at 50°C. HPLC assay at this point shows ⁇ 0.5A% of the amide remaining. The amide is not removed in the isolation so it is important to push the reaction to completion.
  • the reaction slurry is cooled to 0-5°C and quenched by addition of 5% aqueous sodium carbonate solution (1 L) and heptane (1 L). The layers are stirred and separated and the organic is washed with water (300 mL).
  • HPLC assay at this point shows the acetonide in >98A% and >90% yield.
  • the acetonide/THF/heptane solution is filtered into a 2 L round bottom flask and the solution is distilled to a final volume of 700mL.
  • Heptane (1L) is added and the solution is distilled to a final volume of 700mL.
  • the distillation is done under partial vacuum at ⁇ 50°C.
  • NMR assay at this point shows ⁇ 2 mol% THF.
  • the solution is allowed to cool and is seeded with acetonide at 35-40°C.
  • the thick slurry is aged for 1 hour at ambient temperature then cooled to 0-5°C and aged for 1 hour.
  • the slurry is filtered and the cake is washed with cold heptane (200 mL) and air dried to yield acetonide as a crystalline white solid (141.1 g, 85% yield, 99.6 A%).
  • a THF solution (2L, KF ⁇ 200 ⁇ g/mL) of the acetonide (252 g) and the benzyl chloride (255 g) is cooled to -10°C.
  • Lithium bis(trimethylsilyl)amide (1.45 L) is added dropwise over 5 h at 0-2°C.
  • the mixture is then aged for 1.5 h and assayed by HPLC.
  • the reaction is quenched by adding aqueous saturated ammonium chloride solution (1 L).
  • the initial addition of the ammonium chloride should be slow in order to control the foaming. The rate can be increased when the foaming subsides.
  • the quenched reaction is then transfered into a mixture of aqueous ammonium chloride (1.5 L), water (0.5 L), and ethyl acetate (3 L). The mixture is then agitated for 15 min and the layers are separated. The organic layer is washed with water (1 L) and brine (0.5 L). The ethyl acetate solution is concentrated to a low volume and solvent switched to 1,4-dioxane. The dioxane solution is adjusted to a final volume of 1.8 L. The dioxane solution of the coupled product is charged to a
  • the mixture is cooled to 20°C and MTBE (3 L) is added. The mixture is agitated for 15 min and the layers are separated. The organic layer is washed with water (1 L).
  • the MTBE solution of the crude acid is extracted with 0.6 M sodium hydroxide (2 L).
  • the aqueous solution of the sodium salt of the acid is combined with MTBE (2.5 L) and cooled to 10°C.
  • the two phase mixture is acidified with 5.4 M sulfuric acid (250 mL), agitated for 15 min, settled and the layers separated.
  • the MTBE solution of the acid is washed with water (0.5 L).
  • the MTBE solution of the acid is dried by distilation and then solvent switched to THF.
  • the final volume of the THF is 2 L with a KF ⁇ 250 ⁇ g/mL.
  • THF solution (2 L) of the acid is added to the sodium borohydride slurry over 1 h while maintaining the temperature at 20-25°C.
  • reaction is controlled with a cooling bath and by carefully monitoring the addition rate. A nitrogen sweep and proper venting of the hydrogen is also important.
  • the mixture is aged for 30 min at 20-25 °C.
  • Boron trifluoride etherate (152 g) is added over 1 h at 30-35 °C. The addition produces a delayed exotherm and should be carefully monitored in order to control the reaction temperature.
  • the resulting milky white slurry is aged for 1 h at 30 °C and sampled for HPLC assay.
  • reaction mixture is cooled to 15 °C and carefully quenched in a cold (10°C) ammonium chloride solution (1.5 L) while maintaing the temperature at 25 °C.
  • the rate of hydrogen evolution is controlled by the rate of the addition of the mixture into the ammonium chloride.
  • the quenched mixture is distilled in vacuo to remove the
  • the aqueous layer is extracted with MTBE (1.5 L) and the organic layer is dried by flushing with additional MTBE.
  • the MTBE solution is then solvent switched to hexanes and adjusted to a volume of 350 mL and seeded.
  • the slurry is aged for 2 h at 20 °C and then cooled to 0-5 °C aged for 1 h and filtered.
  • the cake is washed with cold hexanes (200 mL).
  • the solid is dried under a nitrogen sweep.
  • the isolated solid (164 g) is > 99A% by HPLC and > 99%ee. 20
  • the acid was prepared following the general procedure recited in Example 1.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention concerne l'oxydation d'un alcool primaire représenté par la formule II en l'acide carboxylique représenté par la formule (I): R1CH2OH→R1CO2H.
EP99916376A 1998-04-09 1999-04-05 Procede d'oxydation au moyen de tempo Withdrawn EP1070039A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US8120298P 1998-04-09 1998-04-09
US81202P 1998-04-09
GB9810188 1998-05-13
GBGB9810188.4A GB9810188D0 (en) 1998-05-13 1998-05-13 Oxidation process using TEMPO
PCT/US1999/007466 WO1999052849A1 (fr) 1998-04-09 1999-04-05 Procede d'oxydation au moyen de tempo

Publications (1)

Publication Number Publication Date
EP1070039A1 true EP1070039A1 (fr) 2001-01-24

Family

ID=26313666

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99916376A Withdrawn EP1070039A1 (fr) 1998-04-09 1999-04-05 Procede d'oxydation au moyen de tempo

Country Status (5)

Country Link
EP (1) EP1070039A1 (fr)
JP (1) JP2002511440A (fr)
AU (1) AU748207B2 (fr)
CA (1) CA2327890A1 (fr)
WO (1) WO1999052849A1 (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001034657A1 (fr) * 1999-11-08 2001-05-17 Sca Hygiene Products Zeist B.V. Procede d'oxydation d'alcools primaires
JP2002371044A (ja) * 2001-04-11 2002-12-26 Ajinomoto Co Inc β−アミノ−α−ヒドロキシカルボン酸の製造方法
US20050075270A1 (en) * 2001-08-21 2005-04-07 Atsuhiko Zanka Process for preparation of piperidin-2-ylacetic acid
US6426418B1 (en) * 2001-11-02 2002-07-30 Apotex, Inc. Processes for the manufacturing of 3-hydroxy-N,1,6-trialkyl-4-oxo-1,4-dihydropyridine-2-carboxamide
DE10206619B4 (de) * 2002-02-15 2004-03-25 Consortium für elektrochemische Industrie GmbH Verfahren zur Herstellung von Alkincarbonsäuren und Alkincarbonsäure-Alkinalkoholestern durch Oxidation von Alkinalkoholen
DE10244633B3 (de) * 2002-09-25 2004-02-26 Consortium für elektrochemische Industrie GmbH Verfahren zur Herstellung von Alkincarbonsäuren durch Oxidation von Alkinalkoholen
DE102004019376A1 (de) * 2004-04-21 2005-11-10 Wacker-Chemie Gmbh Verfahren zur Herstellung von Carboxyreste aufweisenden Organosiliciumverbindungen
JP5274764B2 (ja) * 2006-11-08 2013-08-28 広栄化学工業株式会社 Ｎ−置換−ホルミルポリメチレンイミンの製造方法
CN101874043A (zh) * 2007-11-26 2010-10-27 国立大学法人东京大学 纤维素纳米纤维及其制造方法、纤维素纳米纤维分散液
GB0918616D0 (en) 2009-10-23 2009-12-09 3M Innovative Properties Co Method of preparing highly fluorinated carboxylic acids and their salts
WO2013078172A1 (fr) * 2011-11-23 2013-05-30 The United States Of America As Represented By The Secretary Of The Navy Glycoconjugaison médiée par tempo d'une composition immunogène contre campylobacter jejuni
CN104557579B (zh) * 2014-12-09 2017-02-22 杭州海尔希畜牧科技有限公司 一种制备甜菜碱的方法
WO2023151894A1 (fr) 2022-02-11 2023-08-17 Henkel Ag & Co. Kgaa Méthode de synthèse d'alpha-méthylène-gamma-butyrolactone

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5631366A (en) * 1995-01-12 1997-05-20 Hoffmann-La Roche Inc. Process for making 3-formylcephem derivatives

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9952849A1 *

Also Published As

Publication number Publication date
CA2327890A1 (fr) 1999-10-21
JP2002511440A (ja) 2002-04-16
WO1999052849A1 (fr) 1999-10-21
AU748207B2 (en) 2002-05-30
AU3471199A (en) 1999-11-01

Similar Documents

Publication Publication Date Title
Kozikowski et al. Methods for the stereoselective cis-cyanohydroxylation and-carboxyhydroxylation of olefins
US6127573A (en) Oxidaton of primary alcohols to carboxylic acids with a TEMPO catalyst using NaClO2 and NaClO
Cava et al. Condensed cyclobutane aromatic compounds. XXVI. Benzocyclobutadienoquinone: synthesis and simple transformations
AU748207B2 (en) Oxidation process using tempo
BE1003843A4 (fr) Procede stereospecifique pour la preparation des enantiomeres de la furo (3,4-c) pyridine et composes ainsi obtenus.
AU747500B2 (en) Oxidation process using periodic acid
US5284973A (en) Method of preparing an acid additional salt of delta-aminolevulinic acid
US6150554A (en) Oxidation process using periodic acid
Shimizu et al. One-step oxidation of olefins into. ALPHA.-phenylseleno carbonyl compounds.
JPH08311025A (ja) ４−ヒドロキシ−２−ピロリドンの製法
US4581173A (en) Production of hydroxymethylbutenoic acids via oxidation
CH622808A5 (fr)
KATAOKA et al. Synthesis and Reactions of 10-Chloro-10, 9-(epoxyalkano) selenoxanthenes and 1-Chloro-1-phenyl-3H-2, 1-benzoxaselenoles
EP0362309B1 (fr) (ethylenedioxo-3,3 cyclohexyl)-4 acetophenone et derives de ce compose, procedes pour leur preparation et utilisation de ces composes
EP0464218B1 (fr) Procede de production de derive d'isoxazole
JP3148226B2 (ja) イソキサゾール―４，５―ジカルボン酸ジエステルの製法及びこの種のジエステル
JP3313820B2 (ja) 環式カルボン酸およびエステルの製法
JPH06172297A (ja) ヒドロキシカルボニル誘導体およびその製造方法
JP3249847B2 (ja) Ｚ−シクロヘキシリデン酢酸誘導体の製造方法
KR100786371B1 (ko) 갈란타민의 제조방법
JPH0236592B2 (fr)
JPH03112939A (ja) シクロペンタン類
JPS5839137B2 (ja) アルフア− − ジオ−ル − ガンマ− ジオキソカゴウブツノセイホウ
JPS58121260A (ja) １−アジドシクロプロパンカルボン酸誘導体及びその製造方法
JPH0137382B2 (fr)

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20001109

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU NL PT SE

AX Request for extension of the european patent

Free format text: AL PAYMENT 20001109;LT PAYMENT 20001109;LV PAYMENT 20001109;MK PAYMENT 20001109;RO PAYMENT 20001109;SI PAYMENT 20001109

18W Application withdrawn

Effective date: 20031230

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

R18W Application withdrawn (corrected)

Effective date: 20031230