WO2003070678A1 - Iodination of 4-fluoro-benzaldehyde - Google Patents
Iodination of 4-fluoro-benzaldehyde Download PDFInfo
- Publication number
- WO2003070678A1 WO2003070678A1 PCT/US2003/003082 US0303082W WO03070678A1 WO 2003070678 A1 WO2003070678 A1 WO 2003070678A1 US 0303082 W US0303082 W US 0303082W WO 03070678 A1 WO03070678 A1 WO 03070678A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acid
- fluoro
- benzaldehyde
- inorganic
- iodination
- Prior art date
Links
- DGUYWJGDFCRUHC-UHFFFAOYSA-N O=Cc(cc1I)ccc1F Chemical compound O=Cc(cc1I)ccc1F DGUYWJGDFCRUHC-UHFFFAOYSA-N 0.000 description 2
- REROQYYZGYOCBU-UHFFFAOYSA-N Nc1cc(CO)ccc1F Chemical compound Nc1cc(CO)ccc1F REROQYYZGYOCBU-UHFFFAOYSA-N 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N O=Cc(cc1)ccc1F Chemical compound O=Cc(cc1)ccc1F UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- KUENOVPEGWQHMJ-UHFFFAOYSA-N OCc(cc1I)ccc1F Chemical compound OCc(cc1I)ccc1F KUENOVPEGWQHMJ-UHFFFAOYSA-N 0.000 description 1
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)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2003569588A JP2005525350A (en) | 2002-02-19 | 2003-02-03 | Iodination of 4-fluoro-benzaldehyde |
EP03742706A EP1476415A1 (en) | 2002-02-19 | 2003-02-03 | Iodination of 4-fluoro-benzaldehyde |
MXPA04008072A MXPA04008072A (en) | 2002-02-19 | 2003-02-03 | Iodination of 4-fluoro-benzaldehyde. |
CA002476824A CA2476824A1 (en) | 2002-02-19 | 2003-02-03 | Iodination of 4-fluoro-benzaldehyde |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US7861702A | 2002-02-19 | 2002-02-19 | |
US10/078,617 | 2002-02-19 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2003070678A1 true WO2003070678A1 (en) | 2003-08-28 |
Family
ID=27752716
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2003/003082 WO2003070678A1 (en) | 2002-02-19 | 2003-02-03 | Iodination of 4-fluoro-benzaldehyde |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1476415A1 (en) |
JP (1) | JP2005525350A (en) |
CA (1) | CA2476824A1 (en) |
MX (1) | MXPA04008072A (en) |
WO (1) | WO2003070678A1 (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5248489B2 (en) * | 2007-05-18 | 2013-07-31 | 日宝化学株式会社 | Method for producing halogenated aromatic compound |
JP5295613B2 (en) * | 2008-04-07 | 2013-09-18 | 日宝化学株式会社 | Process for producing iodinated aromatic compounds |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999031059A1 (en) * | 1997-12-18 | 1999-06-24 | Abbott Laboratories | Potassium channel openers |
-
2003
- 2003-02-03 CA CA002476824A patent/CA2476824A1/en not_active Abandoned
- 2003-02-03 JP JP2003569588A patent/JP2005525350A/en not_active Withdrawn
- 2003-02-03 WO PCT/US2003/003082 patent/WO2003070678A1/en not_active Application Discontinuation
- 2003-02-03 MX MXPA04008072A patent/MXPA04008072A/en unknown
- 2003-02-03 EP EP03742706A patent/EP1476415A1/en not_active Withdrawn
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999031059A1 (en) * | 1997-12-18 | 1999-06-24 | Abbott Laboratories | Potassium channel openers |
Non-Patent Citations (2)
Title |
---|
CHEMICAL ABSTRACTS, vol. 134, Columbus, Ohio, US; abstract no. 266060, CHAIKOVSKI, VITOLD K. ET AL: "N-Iodoimines in H2SO4 as the most powerful iodination agents for deactivated arenes" XP001081847 * |
PROCEEDINGS - KORUS 2000, THE KOREA-RUSSIA INTERNATIONAL SYMPOSIUM ON SCIENCE AND TECHNOLOGY, 4TH, ULSAN, REPUBLIC OF KOREA, JUNE 27-JULY 1, 2000 (2000), VOLUME 1, 192-195 PUBLISHER: INSTITUTE OF ELECTRICAL AND ELECTRONICS ENGINEERS, NEW YORK, N. Y. * |
Also Published As
Publication number | Publication date |
---|---|
CA2476824A1 (en) | 2003-08-28 |
JP2005525350A (en) | 2005-08-25 |
MXPA04008072A (en) | 2004-11-26 |
EP1476415A1 (en) | 2004-11-17 |
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