EP2841424A1 - Procédé pour la synthèse de 4-méthyloxazole-5-carboxamide - Google Patents

Procédé pour la synthèse de 4-méthyloxazole-5-carboxamide

Info

Publication number
EP2841424A1
EP2841424A1 EP13719475.9A EP13719475A EP2841424A1 EP 2841424 A1 EP2841424 A1 EP 2841424A1 EP 13719475 A EP13719475 A EP 13719475A EP 2841424 A1 EP2841424 A1 EP 2841424A1
Authority
EP
European Patent Office
Prior art keywords
mol
reaction
oxa
aqueous ammonia
mmol
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Withdrawn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
EP13719475.9A
Other languages
German (de)
English (en)
Inventor
Jocelyn Fischesser
Philippe Karrer
Letizia VOLPE
Werner Bonrath
Hongyan Shen
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.)
DSM IP Assets BV
Original Assignee
DSM IP Assets BV
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
Application filed by DSM IP Assets BV filed Critical DSM IP Assets BV
Priority to EP13719475.9A priority Critical patent/EP2841424A1/fr
Publication of EP2841424A1 publication Critical patent/EP2841424A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D263/48—Nitrogen atoms not forming part of a nitro radical

Definitions

  • the present invention provides a process for synthesis of 4-methyl- oxazole-5-carboxamide (OXA) which comprises reacting a compound of formula (I) with a high concentration of aqueous ammonia:
  • Ri is H or Ci-io alkyl.
  • the term "Ci-io alkyl” as used refers to branched or unbranched, cyclic or non-cyclic, saturated alkyl comprising 1 -10 carbon atoms.
  • the "Ci-io alkyl” is C1-4 alkyl, including but limited to methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl, methyl cyclopropyl and cyclobutyl. More preferably, the "Ci-io alkyl” is methyl or ethyl.
  • the present invention provides a process for synthesis of 4-methyl-oxazole-5- carboxamide (OXA) which comprises reacting a compound of formula (I) with a high concentration of aqueous ammonia:
  • Ri is H or Ci-io alkyl.
  • the reaction is carried out in the presence of a catalyst, which may be selected from the group consisting of ammonium salts, quaternary ammonium salts and alkali metal phosphates.
  • a catalyst which may be selected from the group consisting of ammonium salts, quaternary ammonium salts and alkali metal phosphates.
  • the reaction may be conveniently carried out under pressure and temperature conditions typical for reactions in aqueous ammonia and well-known to those skilled in the art.
  • the reaction is carried out at a temperature of 10°C to 25°C, more preferably 20°C, under an atmospheric pressure.
  • the process of the present invention is very simple and has advantages of high yield (up to 97%), short reaction time (about 10 hours), and short crystallization time of the produced OXA from the reaction mixture (about 2 hours).
  • the crystals were filtered and dried at 50°C, 20 mbar overnight.
  • the mother liquor was evaporated under reduced pressure (15 mbar, 50°C) and the residue was dried at 50°C, 20 mbar. 17.2 g OXA was obtained with a purity of 99.9 % ( 1 H NMR).
  • the crude yield was 92.3% based on OXE and the selectivity 92.5%.
  • the isolated yield was 68.2 %.
  • Example 9 Preparation of OXA in a mixture of aqueous ammonia and ethanol catalyzed with ammonium chloride starting from purified OXE
  • the reaction mixture was cooled down to -20°C and stirred (300 rpm) during 10 hour.
  • the crystals were filtered and dried at 50°C, 20 mbar overnight.
  • the mother liquor was evaporated under reduced pressure (15 mbar, 50°C) and the residue was dried at 50°C, 20 mbar. 17.2 g OXA was obtained with a purity of 99.9 % ( 1 H NMR).
  • the crude yield was 96.6% based on OXE and the selectivity 97.7%.
  • the isolated yield was 85.4 %.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

La présente invention porte sur un nouveau procédé pour la synthèse de 4-méthyloxazole-5-carboxamide (OXA) qui comprend la réaction d'un composé de formule (I) avec une concentration élevée d'ammoniaque : (I). Dans la formule, R1 représente H ou un groupe alkyle en C1-10.
EP13719475.9A 2012-04-25 2013-04-24 Procédé pour la synthèse de 4-méthyloxazole-5-carboxamide Withdrawn EP2841424A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP13719475.9A EP2841424A1 (fr) 2012-04-25 2013-04-24 Procédé pour la synthèse de 4-méthyloxazole-5-carboxamide

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP12165425 2012-04-25
PCT/EP2013/058426 WO2013160322A1 (fr) 2012-04-25 2013-04-24 Procédé pour la synthèse de 4-méthyloxazole-5-carboxamide
EP13719475.9A EP2841424A1 (fr) 2012-04-25 2013-04-24 Procédé pour la synthèse de 4-méthyloxazole-5-carboxamide

Publications (1)

Publication Number Publication Date
EP2841424A1 true EP2841424A1 (fr) 2015-03-04

Family

ID=48227224

Family Applications (1)

Application Number Title Priority Date Filing Date
EP13719475.9A Withdrawn EP2841424A1 (fr) 2012-04-25 2013-04-24 Procédé pour la synthèse de 4-méthyloxazole-5-carboxamide

Country Status (3)

Country Link
EP (1) EP2841424A1 (fr)
CN (2) CN104203930A (fr)
WO (1) WO2013160322A1 (fr)

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3538110A (en) 1966-11-12 1970-11-03 Basf Ag Production of 4-methyloxazole-5-carboxylic esters
US4026901A (en) 1975-04-30 1977-05-31 Hoffmann-La Roche Inc. Conversion of 4-lower alkyloxazole-5-carboxamide to 4-lower alkyl-5-cyanooxazoles
EP0224706A1 (fr) * 1985-11-01 1987-06-10 F. Hoffmann-La Roche Ag Procédé pour la préparation d'un oxazole
DE59408098D1 (de) * 1993-02-25 1999-05-20 Hoffmann La Roche Verfahren zur Herstellung von Oxazolderivaten
US5910594A (en) 1997-02-13 1999-06-08 Roche Vitamins Inc. Process for the manufacture of 5-cyano-4-lower alkyl-oxazoles
US8067583B2 (en) 2006-12-26 2011-11-29 Trustees Of Dartmouth College Method for synthesizing furanosteroids

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
None *
See also references of WO2013160322A1 *

Also Published As

Publication number Publication date
WO2013160322A1 (fr) 2013-10-31
CN110229115A (zh) 2019-09-13
CN104203930A (zh) 2014-12-10

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