38186-88-8

Basic information

• Product Name: 2-Chloro-5-fluoronicotinic acid
• Synonyms: 3-Pyridinecarboxylic acid, 2-chloro-5-fluoro-;2-Chloro-5-fluoropyridine-3-carboxylic acid, 3-Carboxy-2-chloro-5-fluoropyridine;2-chloro -5-fluorinenicotinic acid;2--5-fluorinechlorinenicotinic acid;2-Chloro-5-fluoropyridine-3-carboxylic acid technical grade;2-CHLORO-5-FLUOROPYRIDINE-3-CARBOXYLIC ACID;2-CHLORO-5-FLUORONICOTINIC ACID;2-chloro-5-fluoronicotinic
• CAS NO: 38186-88-8
• Molecular Formula: C₆H₃ClFNO₂
• Molecular Weight: 175.54
• Product Categories: C5 to C6;C6 to C7;Chemical Synthesis;Fluorinated Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Heterocyclic Fluorinated Building Blocks;Other Fluorinated Heterocycles;Pyridine;Pyridines, Pyrimidines, Purines and Pteredines;pharmacetical;Pyridines;Building Blocks;Boronic Acid
• Mol File: 38186-88-8.mol
• Article Data: 20

Chemical Properties

• Melting Point: 141-142°C
• Boiling Point: 297.003 °C at 760 mmHg
• Flash Point: 133.423 °C
• Appearance: /
• Density: 1.576 g/cm³
• Vapor Pressure: 349mmHg at 25°C
• Refractive Index: 1.313
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 1.67±0.25(Predicted)
• CAS DataBase Reference: 2-Chloro-5-fluoronicotinic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-5-fluoronicotinic acid(38186-88-8)
• EPA Substance Registry System: 2-Chloro-5-fluoronicotinic acid(38186-88-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 7/9-24/25-26-36/37-38-51
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 38186-88-8(Hazardous Substances Data)

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 71, p. 4021, 2006 DOI: 10.1021/jo0602571

InChI:InChI=1/C4H5F3O/c1-2-3(8)4(5,6)7/h2H2,1H3

Upstream product

• 82671-06-5 2,6-dichloro-5-fluoro-3-pyridinecarboxylic acid 
• 139911-30-1 ethyl 2-chloro-5-fluoropyridine-3-carboxylate 
• 1316084-72-6 (2E,4Z)-ethyl 2-cyano-5-(dimethylamino)-4-fluoro-penta-2,4-dienoate 

Downstream Products

• 847728-82-9 methyl 5-fluoro-2-(4-fluorophenoxy)nicotinate 
• 847729-27-5 2-chloro-5-fluoronicotinic acid methyl ester 
• 582332-90-9 anti-{4-[(2-Chloro-5-fluoro-pyridine-3-carbonyl)amino]-cyclohexyl}-carbamic acid tert-butyl ester 
• 884494-33-1 2-chloro-5-fluoro-3-iodo-pyridine 
• 1383485-52-6 C₄₁H₃₄F₂N₆O₂ 
• 1383485-59-3 (2S,3S)-3-(3-fluoro-6-(5-fluoro-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)pyridin-2-ylamino)bicyclo[2.2.2]octane-2-carboxylic acid 
• 581772-25-0 (4-{[(2-chloro-5-fluoro-pyridine-3-carbonyl)-amino]-methyl}-benzyl)-carbamic acid tert-butyl ester 
• 1003872-56-7 2-chloro-N-cyclohexyl-5-fluoro-pyridine-3-carboxamide 

Relevant articles and documents

A practical synthesis of 2-((1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic acid

A practical synthesis of a key pharmaceutical intermediate, 2-[(1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino]-5-fluoronicotinic acid (1), is described. To introduce the aminomethyl moiety of 2 via a palladium-catalyzed cyanation/reduction sequence, a regioselective chlorination of 7-azaindole via the N-oxide was developed. A highly selective monodechlorination of 2,6-dichloro-5-fluoronicotinic acid was discovered to afford the nicotinic acid 3. The two building blocks 2 and 3 were then coupled to complete the preparation of 1.

A one-pot diazotation-fluorodediazoniation reaction and fluorine gas for the production of fluoronaphthyridines

Several synthetic routes to 7-fluoro-2-methoxy-8-methyl-1,5-naphthyridine (1) are presented, and their suitability for scale-up is discussed. The way of introducing the fluorine atom is crucial. Early routes start from commercially available fluorinated building blocks or employ F+ reagents like SelectFluor and delivered up to 70 kg of 7-fluoro-2-methoxy-1,5-naphthyridine (18). To prepare for larger scales, the focus turned to the use of HF or elemental fluorine, both one of the cheapest sources of fluorine. The first method, a one-pot diazotation-fluorodediazoniation with 6-methoxy-1,5- naphthyridin-3-amine (9) in HF gave the fluorinated naphthyridine 18 in high yield and purity without isolation of the unstable diazonium salt, the latter being a severe drawback of the related Balz-Schiemann protocol. The second method relies on the use of fluorine gas for a surprisingly selective ortho-fluorination of 6-methoxy-1,5-naphthyridin-4-ol (10).

A modified approach to C-14-labeled 2-(3,4-difluorophenoxy)-5- fluoronicotinic acid and other halogen-substituted analogs

A modified approach to a carbon-14-labeled pyridine ring system was developed based on the electrocyclic ring-closure of 1,4,4-trisubstituted butadiene. The new method was applied to prepare 2-(3,4-difluorophenoxy)-5- fluoro-[2-14C] nicotinic a