| Identification | More | [Name]
2-Chloro-5-fluoronicotinic acid | [CAS]
38186-88-8 | [Synonyms]
2-CHLORO-5-FLUORONICOTINIC ACID
2-CHLORO-5-FLUOROPYRIDINE-3-CARBOXYLIC ACID
2-chloro-5-fluoronicotinic | [Molecular Formula]
C6H3ClFNO2 | [MDL Number]
MFCD03092932 | [Molecular Weight]
175.54 | [MOL File]
38186-88-8.mol |
| Chemical Properties | Back Directory | [Melting point ]
141-142°C | [Boiling point ]
297.0±35.0 °C(Predicted) | [density ]
1.576±0.06 g/cm3(Predicted) | [storage temp. ]
Inert atmosphere,2-8°C | [form ]
powder | [pka]
1.67±0.25(Predicted) | [color ]
Off-white | [InChI]
InChI=1S/C6H3ClFNO2/c7-5-4(6(10)11)1-3(8)2-9-5/h1-2H,(H,10,11) | [InChIKey]
WMADTZFXZAITIR-UHFFFAOYSA-N | [SMILES]
C1(Cl)=NC=C(F)C=C1C(O)=O | [CAS DataBase Reference]
38186-88-8(CAS DataBase Reference) |
| Questions And Answer | Back Directory | [Application]
2-Chloro-5-fluoronicotinic acid possesses unique chemical properties and pharmaceutical activity, making it an intermediate in many pharmaceuticals and pesticides with a very broad application prospect. It can also be used as a pharmaceutical and pharmaceutical intermediate, a hair dyeing auxiliary agent, a polymer stabilizer, an antioxidant in photosensitive materials, and an anti-fogging agent, among other applications. 2-Chloro-5-fluoronicotinic acid is also an intermediate in many high-value-added drugs, including diabetes medications, antidepressants, antitumor drugs, local anesthetics, and antihypertensive drugs, and it has applications in the fields of antihypertensive, antitumor, and anticoccosis treatments. |
| Hazard Information | Back Directory | [Synthesis Reference(s)]
The Journal of Organic Chemistry, 71, p. 4021, 2006 DOI: 10.1021/jo0602571 | [Synthesis]
The general procedure for the synthesis of 2-chloro-5-fluoronicotinic acid from 2,6-dichloro-5-fluoropyridine-3-carboxylic acid is as follows:
1. Synthesis of the intermediate 5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-amine:
- Reagents and conditions:
i. Pd(OAc)2, PPh3, Et3N, HCOOH.
ii. 1) (COCl)2, CH2Cl2, catalytic amount of DMF; 2) NH3(g), Dioxane; iii.
iii. TFAA, Et3N, CH2Cl2, 0 °C.
H2NNH2-H2O, n-butanol, reflux. iv.
2. Synthesis of 2-chloro-5-fluoronicotinic acid (6):
- Degassed DMF (270 μL), Pd(OAc)2 (0.05 eq, 2.7 g, 11.9 mmol), PPh3 (0.1 eq, 6.2 g, 23.8 mmol), and degassed Et3N (6 eq, 200 mL, 1428.6 mmol) were added to a round-bottomed flask under N2 atmosphere.
- The mixture was stirred for 20 min and then HCOOH (3 eq, 28 mL, 714.3 mmol) was added.
- After 5 min, 2,6-dichloro-5-fluoronicotinic acid (50 g, 238.1 mmol) was added.
- The mixture was stirred at 50 °C and the progress of the reaction was monitored by 1H NMR analysis.
- When all ingredients were consumed (~24 h), the mixture was cooled to 0 °C and water (500 mL) was added.
- After 20 minutes, the mixture was filtered through a diatomaceous earth pad and rinsed with water.
- The mixture was alkalized to pH 9 with 30% NaOH aqueous solution and then washed with EtOAc (2x).
- 12N HCl was added slowly to pH 1 and treated with a saturated solution of NaCl.
- The mixture was extracted with EtOAc (3x), the organic phases were combined, washed with brine, dried (Na2SO4), and concentrated under reduced pressure to give 37 g (88% yield) of a beige solid, which could be used in the next step without further purification.
- 1H NMR (DMSO-d6, 300MHz): δ 8.16 (dd, 1H); 8.58 (d, 1H). | [References]
[1] Patent: WO2008/77086, 2008, A1. Location in patent: Page/Page column 56-57
[2] Patent: WO2009/18415, 2009, A1. Location in patent: Page/Page column title page; 35
[3] Patent: WO2008/112642, 2008, A1. Location in patent: Page/Page column 50; 50-51
[4] Patent: WO2008/112646, 2008, A1. Location in patent: Page/Page column 49-50
[5] Patent: WO2009/145814, 2009, A2. Location in patent: Page/Page column 49 |
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