EP1476415A1 - Iodierung von 4-fluorbenzaldehyd - Google Patents

Iodierung von 4-fluorbenzaldehyd

Info

Publication number
EP1476415A1
EP1476415A1 EP03742706A EP03742706A EP1476415A1 EP 1476415 A1 EP1476415 A1 EP 1476415A1 EP 03742706 A EP03742706 A EP 03742706A EP 03742706 A EP03742706 A EP 03742706A EP 1476415 A1 EP1476415 A1 EP 1476415A1
Authority
EP
European Patent Office
Prior art keywords
acid
fluoro
benzaldehyde
inorganic
iodination
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Withdrawn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
EP03742706A
Other languages
English (en)
French (fr)
Inventor
Steven J. Wittenberger
Sou-Jen Chang
Gregory S. Wayne
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.)
Abbott Laboratories
Original Assignee
Abbott Laboratories
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 Abbott Laboratories filed Critical Abbott Laboratories
Publication of EP1476415A1 publication Critical patent/EP1476415A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms

Definitions

  • Potassium channels play an important role in regulating cell membrane excitability.
  • Such diseases or conditions include asthma, epilepsy, male sexual dysfunction, female sexual dysfunction, pain, bladder overactivity, stroke, diseases associated with decreased skeletal blood flow such as Raynaud's phenomenon and intermittent claudication, eating disorders, functional bowel disorders, neurodegeneration, benign prostatic hyperplasia (BPH), dysmenorrhea, premature labor, alopecia, cardioprotection, coronary artery disease, angina, ischemia, and incontinence.
  • diseases or conditions include asthma, epilepsy, male sexual dysfunction, female sexual dysfunction, pain, bladder overactivity, stroke, diseases associated with decreased skeletal blood flow such as Raynaud's phenomenon and intermittent claudication, eating disorders, functional bowel disorders, neurodegeneration, benign prostatic hyperplasia (BPH), dysmenorrhea, premature labor, alopecia, cardioprotection, coronary artery disease, angina, ischemia, and incontinence.
  • BPH benign prostatic hyperplasia
  • dysmenorrhea premature labor
  • alopecia
  • 4-fluoro-3-iodo-benzaldehyde was previously synthesized in five steps as shown in Scheme 1.
  • 4-fluorobenzoic acid (1) is converted to 4-fluoro-3-nitrobenzoic acid (2) which is then reduced to the corresponding amine (3). Further reduction results in the alcohol (4) and subsequent iodination (5) and oxidation ultimately leads to the iodinated benzaldehyde (6).
  • the present invention relates to a process for producing an intermediate that is used to make a dihydropyridine potassium channel opener.
  • the present invention relates to an efficient synthesis of 4-fluoro-3-iodo-benzaldehyde by iodinating 4-fluoro-benzaldehyde.
  • 4-Fluoro-3-iodo-benzaldehyde is a key intermediate in the manufacture of the potassium channel opener, 5-(4-fluoro-3-iodophenyl)-5,10 dihydro-lH,3H- dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H) dione.
  • the present invention relates to an improved process for iodinating benzaldehydes.
  • the improved process allows for a one- step procedure for synthesizing 4- fluoro-3-iodo-benzaldehyde.
  • 4-Fluoro-3-iodobenzaldehyde is synthesized by combining 4- fluorobenzaldehyde and N-iodosuccinimide in an acid medium.
  • the 4-Fluoro-3- iodobenzaldehyde and N-iodosuccinimide are in a 1 : 1.2 equivalents ratio respectively.
  • Suitable acids for use in the present invention include organic acids and inorganic acids.
  • An example of organic acids suitable for use in the present invention includes, but is not intended to be limited to, trifluoromethanesulfonic acid.
  • Inorganic acids are suitable for use in the present invention as well.
  • Inorganic acids suitable for use in the present invention include, but is not intended to be limited to, nitric acid, sulfuric acid, and hydrochloride acid.
  • the inorganic acid may be used in combination with acetic acid as well.
  • Acetic acid is used for solubility purposes.
  • a strong inorganic acid/acetic acid combination is suitable for use in the present invention.
  • the inorganic acid/acetic acid combination is in a 1:1 ratio.
  • the wetcake was dissolved in 380 g ethyl acetate / heptane (1:1 v/v containing 250 ppm BHT) and the solution was washed with 10% aqueous sodium thiosulfate (204 g), then with 10% aqueous sodium carbonate (214 g), followed by 200 g water.
  • the solution was concentrated to approximately 40 mL, and 148 g heptane (containing

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
EP03742706A 2002-02-19 2003-02-03 Iodierung von 4-fluorbenzaldehyd Withdrawn EP1476415A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US78617 1987-07-28
US7861702A 2002-02-19 2002-02-19
PCT/US2003/003082 WO2003070678A1 (en) 2002-02-19 2003-02-03 Iodination of 4-fluoro-benzaldehyde

Publications (1)

Publication Number Publication Date
EP1476415A1 true EP1476415A1 (de) 2004-11-17

Family

ID=27752716

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03742706A Withdrawn EP1476415A1 (de) 2002-02-19 2003-02-03 Iodierung von 4-fluorbenzaldehyd

Country Status (5)

Country Link
EP (1) EP1476415A1 (de)
JP (1) JP2005525350A (de)
CA (1) CA2476824A1 (de)
MX (1) MXPA04008072A (de)
WO (1) WO2003070678A1 (de)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008143141A1 (ja) * 2007-05-18 2008-11-27 Nippoh Chemicals Co., Ltd. ハロゲン化芳香族化合物の製造方法
JP5295613B2 (ja) * 2008-04-07 2013-09-18 日宝化学株式会社 ヨウ素化芳香族化合物の製造方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUP0100112A3 (en) * 1997-12-18 2004-05-28 Abbott Lab Fused pyridine derivatives having potassium chanel opening activity and their use

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03070678A1 *

Also Published As

Publication number Publication date
CA2476824A1 (en) 2003-08-28
MXPA04008072A (es) 2004-11-26
WO2003070678A1 (en) 2003-08-28
JP2005525350A (ja) 2005-08-25

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