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WO2006062477A1 - Procede chimique - Google Patents

Procede chimique Download PDF

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Publication number
WO2006062477A1
WO2006062477A1 PCT/SE2005/001865 SE2005001865W WO2006062477A1 WO 2006062477 A1 WO2006062477 A1 WO 2006062477A1 SE 2005001865 W SE2005001865 W SE 2005001865W WO 2006062477 A1 WO2006062477 A1 WO 2006062477A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
acetic acid
zinc
dichloro
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/SE2005/001865
Other languages
English (en)
Inventor
Matthew Perry
Brian Springthorpe
Linda Stein
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.)
AstraZeneca AB
Original Assignee
AstraZeneca AB
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 AstraZeneca AB filed Critical AstraZeneca AB
Publication of WO2006062477A1 publication Critical patent/WO2006062477A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/14—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of a —CHO group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
    • C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/23—Preparation of halogenated hydrocarbons by dehalogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C25/00—Compounds containing at least one halogen atom bound to a six-membered aromatic ring
    • C07C25/02—Monocyclic aromatic halogenated hydrocarbons
    • C07C25/13—Monocyclic aromatic halogenated hydrocarbons containing fluorine

Definitions

  • the present invention concerns a process for the preparation of 3-methyl-l,2- dichloro-4-fluorobenzene.
  • 3-Methyl-l,2-dichloro-4-fluorobenzene is useful in the preparation of modulators (for example antagonists) of CCR3 chemokine receptor activity.
  • modulators for example antagonists
  • 3-methyl- l,2-dichloro-4-fluorobenzene is a useful pharmaceutical intermediate in the preparation of [(phenoxy)-[l,4']bipiperidinyl-r-yl] derivatives (see, for example, WO 03/004487, WO2004/099144 and WO2004/087659).
  • the present invention provides a process for the preparation of a compound of formula (I):
  • the present invention provides a process for preparing a compound of formula (I), the process comprising: a. reacting a compound of formula (II):
  • X is halogen (such as bromo or iodo); and, e. reducing compound or formula (V) with zinc and acetic acid to produce a compound of formula (I).
  • Suitable strong bases are, for example, C 1-1 O alkyl (for example Ci -6 alkyl, such as C 4 ) lithiums (such as «-butyl lithium or .sec-butyl lithium), a di-Ci -10 alkyl (for example di- C 1-6 alkyl) lithium amide base (such as lithium diwo-propylamide), an aryl lithium (such as a phenyl lithium) or an arylalkyl lithium (such as a benzyl lithium).
  • C 1-1 O alkyl for example Ci -6 alkyl, such as C 4
  • lithiums such as «-butyl lithium or .sec-butyl lithium
  • a di-Ci -10 alkyl for example di- C 1-6 alkyl
  • lithium amide base such as lithium diwo-propylamide
  • an aryl lithium such as a phenyl lithium
  • an arylalkyl lithium such as a benzyl lithium
  • a suitable strong base is, for example a C 1-6 alkyl (such as a C 1-4 alkyl, for example a C 4 ) lithium (such as «-butyl lithium or sec-butyl lithium) or a di-Ci -6 alkyl lithium amide base (such as lithium diwo-propylamide).
  • the strong base is «-butyl lithium.
  • a suitable solvent for formation of an aldehyde of formula (III) from a compound of formula (II) is an ether (for example tetrahydrofuran [THF], methyl fert-butyl ether or dioxan).
  • Suitable halogenating agents for the preparation of a compound of formula (V) include: trimethylsilyl iodide; triphenylphosphine and iodine (for example using acetonitrile as solvent); thionyl bromide; and, hydrogen bromide in acetic acid.
  • the reduction with zinc and acetic acid is suitably carried out by slowly (typically over 0.5 h) adding the compound of formula (V) to the mixture of zinc and acetic acid.
  • the halogenation of a compound of formula (IV) uses hydrogen bromide in acetic acid then the reduction with zinc and acetic acid can be conducted by adding the reaction mixture resulting from the halogenation reaction directly to zinc in acetic acid.
  • the reduction with zinc and acetic acid is conducted at low concentration (for example by having a slow addition of the compound (V)) to minimise Wurtz-type coupling.
  • the compound of formula (V) is extracted from reaction mixture of the reduction with zinc and acetic acid by extraction of the reaction mixture with pentane and then evaporation of the pentane to leave the title compound.
  • the present invention provides a process as hereinbefore described wherein between 1 and 1.5 molar equivalents of strong base is used ⁇ for example between 1.3 equivalents of strong base ⁇ .
  • the present invention provides a process as hereinbefore described wherein between 0.3 and 0.6 molar equivalents (for example 0.35 to 0.45 molar equivalents) alkali metal borohydride are used.
  • Triphenylphosphine (3.22 g), imidazole (0.84 g) and iodine (3.12 g) were added, in that order, to acetonitrile (20 mL).
  • a solution of (2,3-dichloro-6-fluorophenyl)methanol (2 g) in acetonitrile (10 mL) was added and the mixture was stirred at room temperature, under nitrogen, for 0.5 h.
  • LC/MS showed that all of the starting alcohol had been consumed and a new peak, believed to be the benzyl iodide had appeared; retention time 2.71 minutes on standard gradient.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un procédé de préparation d'un composé représenté par la formule (I), ledit procédé consistant a) à réduire l'aldéhyde représenté par la formule (III) avec du borohydrure de métal alcalin dans de l'éthanol afin d'obtenir un composé représenté par la formule (IV), b) à halogéner un composé représenté par la formule (IV) avec un agent d'halogénation afin de former un composé représenté par la formule (V) dans laquelle X est halogène, et c) à réduire le composé représenté par la formule (V) avec du zinc et de l'acide acétique afin d'obtenir un composé représenté par la formule (I).
PCT/SE2005/001865 2004-12-09 2005-12-07 Procede chimique Ceased WO2006062477A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE0403004A SE0403004D0 (sv) 2004-12-09 2004-12-09 Chemical compound II
SE0403004-5 2004-12-09

Publications (1)

Publication Number Publication Date
WO2006062477A1 true WO2006062477A1 (fr) 2006-06-15

Family

ID=33550626

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE2005/001865 Ceased WO2006062477A1 (fr) 2004-12-09 2005-12-07 Procede chimique

Country Status (2)

Country Link
SE (1) SE0403004D0 (fr)
WO (1) WO2006062477A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109311786A (zh) * 2016-05-02 2019-02-05 陶氏环球技术有限责任公司 芳族氟化的方法
CN111196750A (zh) * 2018-11-20 2020-05-26 清华大学 一种苄碘及其衍生物的制备方法
CN112142544A (zh) * 2019-06-27 2020-12-29 中国科学院上海有机化学研究所 一种卤化物氢解的方法
CN112898273A (zh) * 2021-03-30 2021-06-04 海南锦瑞制药有限公司 伏立康唑的合成方法及应用

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LEROUX F. ET AL: "N-(4-Biphenylmethyl)imidazoles as Potential Therapeutics for the Treatment of Prostate Cancer: Metabolic Robustness Due to Fluorine Substitution?", HELVETICA CHIMICA ACTA, vol. 86, 2003, pages 2671 - 2686, XP002996593 *
PASHA M.A. ET AL: "Zinc metal assisted hydro-de-halogenation of DDT into DDEthane under sonic conditions", INDIAN JOURNAL OF CHEMISTRY, vol. 41B, August 2002 (2002-08-01), pages 1747 - 1748, XP002996594 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109311786A (zh) * 2016-05-02 2019-02-05 陶氏环球技术有限责任公司 芳族氟化的方法
CN109311786B (zh) * 2016-05-02 2021-12-03 陶氏环球技术有限责任公司 芳族氟化的方法
CN111196750A (zh) * 2018-11-20 2020-05-26 清华大学 一种苄碘及其衍生物的制备方法
CN111196750B (zh) * 2018-11-20 2020-11-10 清华大学 一种苄碘及其衍生物的制备方法
CN112142544A (zh) * 2019-06-27 2020-12-29 中国科学院上海有机化学研究所 一种卤化物氢解的方法
CN112142544B (zh) * 2019-06-27 2023-10-27 中国科学院上海有机化学研究所 一种卤化物氢解的方法
CN112898273A (zh) * 2021-03-30 2021-06-04 海南锦瑞制药有限公司 伏立康唑的合成方法及应用

Also Published As

Publication number Publication date
SE0403004D0 (sv) 2004-12-09

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