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WO1998004579A1 - Procede pour la production de derives (ii) de 3-sulfanato-oxy-estra-1,3,5(10)-triene - Google Patents

Procede pour la production de derives (ii) de 3-sulfanato-oxy-estra-1,3,5(10)-triene Download PDF

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Publication number
WO1998004579A1
WO1998004579A1 PCT/EP1997/003707 EP9703707W WO9804579A1 WO 1998004579 A1 WO1998004579 A1 WO 1998004579A1 EP 9703707 W EP9703707 W EP 9703707W WO 9804579 A1 WO9804579 A1 WO 9804579A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
estra
carbon atoms
bonds
trien
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.)
Ceased
Application number
PCT/EP1997/003707
Other languages
German (de)
English (en)
Inventor
Helmut HÄUSER
Michael Meyer
Daniel Ramirez
Maria Elena Rodriguez
Lucia Ibanez
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.)
Bayer Pharma AG
Original Assignee
Schering AG
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 Schering AG filed Critical Schering AG
Priority to AU36228/97A priority Critical patent/AU3622897A/en
Publication of WO1998004579A1 publication Critical patent/WO1998004579A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003

Definitions

  • the invention relates to a process for the preparation of 3-sulfanato-oxy-estra-l, 3,5 (10) -triene derivatives of the general formula I.
  • X denotes a carbonyl group, a hydroxymethylene group, an alkoxymethylene group with 2 to 6 carbon atoms in the alkoxy radical, a benzyloxymethylene group, an acyloxymethylene group with a maximum of 8 carbon atoms in the acyl radical or an alkylenedioxymethylene group with 2 to 6 carbon atoms in the alkylene radical and Z + represents an alkali metal cation, a 3-hydroxy-estra-1,3,5 (10) -triene derivative of the general formula II
  • the alkali metal salts of the general formula I are pharmacologically active substances which are referred to as conjugated estrogens (Pharmacopeia / Forum May, June 1991, p 1951-1962 and J. of Chromatography 224, 1981, p 355-370 and 224, 1982, p 234-239).
  • conjugated estrogens are prepared from the 3-hydroxy-estra-1,3,5 (10) -triene derivatives of the general formula ⁇ in such a way - by combining them with a sulfur trioxide in the presence of sodium hydride -Pyridine complex is implemented (US Pat. Nos. 3,391, 169, 5,210,081 and 5,288,717).
  • the process according to the invention has the advantage that the by-product runs poorer, so that, as a rule, purer process products can be obtained in large-scale processes without expensive cleaning operations in higher yields.
  • reaction of the 3-hydroxy-estra-1,3,5 (10) -triene derivatives of the general formula II with an alkali metal alcoholate and sulfur trioxide-pyridine complex can be carried out in such a way that the
  • the reaction partner is dissolved or suspended in a solvent which is inert to this reagent, optionally with stirring at - 25 ° C to 50 ° C (for the sake of simplicity at room temperature) until completion or reaction.
  • Sodium or potassium alcohols of lower alcohols such as methanol, ethanol, propanol, isopropanol or tert are preferably used as alkali metal alcoholates.
  • Butanol used.
  • Sodium methylate in a concentration of 1.2 to 10.0 mol sodium methylate per mol steroid has proven to be particularly suitable.
  • Suitable inert solvents for this reaction are, for example, polar ethers, such as dioxane, 1,2-dimethoxyethanol or, in particular, tetrahydrofuran.
  • the optimum reaction time is determined in a manner known per se using customary analysis, for example by means of thin-layer or gas chromatography. It is usually 30 minutes to 2 hours.
  • EXAMPLE 2 In an analogous manner, 100.0 g of the sodium salt of 3-sulfanato-oxy-estra-l can be obtained from 100.0 g of Estra-l, 3.5 (10), 7-tetraen-3.17 ⁇ -diol, 3.5 (10), 7-tetraen-17 ⁇ -ol, which contains 7% sodium acetate as stabilizer.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)

Abstract

L'invention concerne un procédé pour produire des dérivés de 3-sulfanato-oxy-estra-1,3,5(10)-triène de la formule générale (I) dans laquelle les liaisons marquées avec le symbole --- symbolisent trois liaisons simples, deux liaisons simples et une liaison double ou bien deux liaisons doubles conjuguées, X désigne un groupe carbonyle, un groupe hydroxyméthylène, un groupe alcoxyméthylène avec 2 à 6 atomes de carbone dans le reste alcoxy, un groupe benzyloxyméthylène, un groupe acyloxyméthylène avec au maximum huit atomes de carbone dans le reste acyle, ou bien un groupe alkylèndioxyméthylène avec 2 à 6 atomes de carbone dans le reste alkylène, et Z+ représente un cation métallique alcalin, en faisant réagir un dérivé de 3-hydroxy-estra-1,3,5(10)-triène, en présence d'un alcoolat de métal alcalin, avec un complexe de trioxyde de soufre-pyridine.
PCT/EP1997/003707 1996-07-25 1997-07-11 Procede pour la production de derives (ii) de 3-sulfanato-oxy-estra-1,3,5(10)-triene Ceased WO1998004579A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU36228/97A AU3622897A (en) 1996-07-25 1997-07-11 Method of producing 3-sulfanato-oxy-estra-1,3,5(10)-trien derivates (ii)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19631542.5 1996-07-25
DE1996131542 DE19631542C1 (de) 1996-07-25 1996-07-25 Verfahren zur Herstellung von 3-Sulfatoxy-estra-1,3,5(10)-trien-Derivaten II

Publications (1)

Publication Number Publication Date
WO1998004579A1 true WO1998004579A1 (fr) 1998-02-05

Family

ID=7801804

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1997/003707 Ceased WO1998004579A1 (fr) 1996-07-25 1997-07-11 Procede pour la production de derives (ii) de 3-sulfanato-oxy-estra-1,3,5(10)-triene

Country Status (3)

Country Link
AU (1) AU3622897A (fr)
DE (1) DE19631542C1 (fr)
WO (1) WO1998004579A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008100769A3 (fr) * 2007-02-09 2009-01-29 Wyeth Corp Procédé de sulfatation sélective de groupements hydroxyles aromatiques

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19631543C1 (de) * 1996-07-25 1997-11-20 Schering Ag Verfahren zur Herstellung von 3-Sulfatoxy-estra-1,3,5(10)-trien-Derivaten I

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2629657A1 (de) * 1975-07-07 1977-01-27 Leo Ab Verfahren zur carbamoylierung von phenolischen hydroxygruppen zwecks herstellung von phenolischen n-disubstituierten carbamatestern und die hierzu verwendeten ionenpaar-loesungen
US4021458A (en) * 1974-04-18 1977-05-03 Schering Aktiengesellschaft Process for the preparation of 3-hemisulfate-17α-hydroxy steroids
WO1993017036A1 (fr) * 1992-02-26 1993-09-02 American Home Products Corporation Esters de sulfate de 8,9-dehydro-estrone de metal alcalin

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3551459A (en) * 1962-10-04 1970-12-29 Herchel Smith 13-methyl-8-isogonanes

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4021458A (en) * 1974-04-18 1977-05-03 Schering Aktiengesellschaft Process for the preparation of 3-hemisulfate-17α-hydroxy steroids
DE2629657A1 (de) * 1975-07-07 1977-01-27 Leo Ab Verfahren zur carbamoylierung von phenolischen hydroxygruppen zwecks herstellung von phenolischen n-disubstituierten carbamatestern und die hierzu verwendeten ionenpaar-loesungen
WO1993017036A1 (fr) * 1992-02-26 1993-09-02 American Home Products Corporation Esters de sulfate de 8,9-dehydro-estrone de metal alcalin

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
H. FEX ET AL: "Hydrogen Sulfates of Natural Estrogens", ACTA CHEMICA SCANDINAVICA., vol. 22, no. 1, 1968, COPENHAGEN DK, pages 254 - 264, XP002044781 *
J. DUSZA ET AL: "The Preparation of Estradiol-17.beta.-Sulfates with Triethylamine-Sulfur Trioxide", STEROIDS., vol. 45, no. 3-4, March 1985 (1985-03-01) - April 1985 (1985-04-01), SAN FRANCISCO US, pages 303 - 315, XP002044784 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008100769A3 (fr) * 2007-02-09 2009-01-29 Wyeth Corp Procédé de sulfatation sélective de groupements hydroxyles aromatiques

Also Published As

Publication number Publication date
AU3622897A (en) 1998-02-20
DE19631542C1 (de) 1997-08-28

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