76041-71-9

Usage

Uses

Used in Pharmaceutical Research:
3-CHLORO-2-HYDROXY-5-(TRIFLUOROMETHYL)PYRIDINE is used as a research chemical for the development of new pharmaceutical compounds. Its unique structure may offer potential applications in the synthesis of novel drugs, particularly in the areas of medicinal chemistry and drug discovery.
Used in Chemical Synthesis:
In the chemical industry, 3-CHLORO-2-HYDROXY-5-(TRIFLUOROMETHYL)PYRIDINE can be used as an intermediate or building block in the synthesis of various organic compounds. Its functional groups may allow for further reactions and modifications, leading to the creation of new molecules with specific properties and applications.
Used in Material Science:
3-CHLORO-2-HYDROXY-5-(TRIFLUOROMETHYL)PYRIDINE may also find applications in material science, where its unique structure could be utilized to develop new materials with specific properties. This could include the creation of advanced polymers, coatings, or other materials with potential uses in various industries.

InChI:InChI=1/C6H4F3NS/c7-6(8,9)4-1-2-5(11)10-3-4/h1-3H,(H,10,11)

Synthetic route

2-hydroxy-5-(trifluoromethyl)pyridine (33252-63-0) → 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9)

Conditions	Yield
With N-chloro-succinimide In 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide at 20℃; for 8h; Solvent;	92%

2,3-dichloro-5-trifluoromethylpyridine (69045-84-7) → 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9)

Conditions	Yield
With potassium hydroxide In tert-butyl alcohol for 1h; Heating;	75.2%

2,3-dichloro-5-(trichloromethyl)pyridine (69045-83-6) → 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80.4 percent / antimony trifluoride / 0.17 h / Heating; Irradiation 2: 75.2 percent / potassium hydroxide / 2-methyl-propan-2-ol / 1 h / Heating View Scheme

6-hydroxy-3-pyridinecarboxylic acid (5006-66-6) → 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen fluoride; sulfur tetrafluoride / 12 h / 100 °C / 1125.11 Torr / Autoclave 2: N-chloro-succinimide / N,N-dimethyl-formamide; 1-methyl-pyrrolidin-2-one / 8 h / 20 °C View Scheme

chloroacetic acid ethyl ester (105-39-5) + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → ethyl 2-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)acetate

Conditions	Yield
With potassium carbonate In acetonitrile Reflux;	94%

tris(3-(diethoxymethyl)phenyl)bismuthine + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → 3-chloro-1-(3-(diethoxymethyl)phenyl)-5-(trifluoromethyl)-2(1H)-pyridinone (1613033-18-3)

Conditions	Yield
With pyridine; copper diacetate In dichloromethane at 50℃; for 16h;	89%

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) + p-toluenesulfonyl chloride (98-59-9) → 3-chloro-5-(trifluoromethyl)-2-pyridinyl tosylate (1174281-15-2)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 1h;	84%

2-(chloromethyl)-5-(4-nitrophenyl)-1,3,4-oxadiazole (50677-30-0) + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → 2-(5-(trifluoromethyl)pyridiloxymethyl)-5-(4-nitrophenyl)-1,3,4-oxadiazole

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide at 90℃;	78%

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) + 2-(chloromethyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole (350672-14-9) → 2-(5-(trifluoromethyl)pyridiloxymethyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide at 90℃;	77%

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) + 5-(2,4-dichloro-5-fluorophenyl)-2-(chloromethyl)-1,3,4-oxadiazole (497182-11-3) → 2-(5-(trifluoromethyl)pyridiloxymethyl)-5-(2,4-dichloro-5-fluorophenyl)-1,3,4-oxadiazole

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide at 90℃;	75%

methyl (E)-3-methoxy-2-(2-chloromethylphenyl)acrylate (117428-51-0) + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → methyl (E)-2-(2-(((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)methyl)phenyl)-3-methoxyacrylate

Conditions	Yield
Stage #1: 3-chloro-5-(trifluoromethyl)-2-hydroxypyridine With potassium carbonate In N,N-dimethyl-formamide for 0.5h; Stage #2: methyl (E)-3-methoxy-2-(2-chloromethylphenyl)acrylate In N,N-dimethyl-formamide at 80℃; for 3h;	74.8%

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) + 2-chloromethyl-5-(4-ethyl-phenyl)-[1,3,4]oxadiazole (350672-18-3) → 2-(5-(trifluoromethyl)pyridiloxymethyl)-5-(4-ethylphenyl)-1,3,4-oxadiazole

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide at 90℃;	74%

{[2-(trifluoromethyl)benzoyl]amino}methyl acetate (895525-72-1) + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → N-({[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-2-(trifluoromethyl)benzamide

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; water at 20℃; for 14h;	74%

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) + methyl (E)-2-[2-(bromomethyl)phenyl]-2-(methoxyimino)acetate (133409-72-0) → methyl (E)-2-(2-(((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetate

Conditions	Yield
Stage #1: 3-chloro-5-(trifluoromethyl)-2-hydroxypyridine With potassium carbonate In butanone for 0.5h; Stage #2: methyl (E)-2-[2-(bromomethyl)phenyl]-2-(methoxyimino)acetate In butanone at 80℃; for 5h;	73.5%

2-(chloromethyl)-5-(4-methoxyphenyl)-1,3,4-oxadiazole (24023-71-0) + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → 2-(5-(trifluoromethyl)pyridiloxymethyl)-5-(4-methoxyphenyl)-1,3,4-oxadiazole

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide at 90℃;	73%

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) + 2-(chloromethyl)-5-phenyl-1,3,4-oxadiazole (33575-83-6) → 2-(5-(trifluoromethyl)pyridiloxymethyl)-5-phenyl-1,3,4-oxadiazole

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide at 90℃;	71%

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) + 2-chloromethyl-5-(2-fluoro-phenyl)-[1,3,4]oxadiazole (350672-17-2) → 2-(5-(trifluoromethyl)pyridiloxymethyl)-5-(2-fluorophenyl)-1,3,4-oxadiazole

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide at 90℃;	70%

2-(chloromethyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole (24068-15-3) + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → 2-(5-(trifluoromethyl)pyridiloxymethyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide at 90℃;	69%

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → 2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7)

Conditions	Yield
With phosphorus(V) oxybromide at 150℃; for 6h; Temperature;	58%

8-chloro-2,2-dimethyl-4-[1,2,4]triazol-1-yloctan-3-one (1217539-63-3) + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → 8-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-2,2-dimethyl-4-[1,2,4]triazol-1-yloctan-3-one (1217539-65-5)

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 180℃; for 0.5h; microwave irradiation;	33%

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) + 3-methyl-1-{[methyl(phenyl)amino]carbonyl}-1H-imidazol-3-ium iodide → methyl-phenyl-carbamic acid 3-chloro-5-trifluoromethyl-pyridin-2-yl ester (548766-54-7)

Conditions	Yield
With triethylamine In acetonitrile	15%

2-[2-(5-fluoro-2-methoxyphenyl)-2-methylpropyl]-2-(trifluoromethyl)oxirane (271587-47-4) + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → 3-chloro-1-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-5-trifluoromethyl-1H-pyridin-2-one (727375-79-3)

Conditions	Yield
With sodium ethanolate In ethanol at 85℃;

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) + cyanomethyl bromide (590-17-0) → N-cyanomethyl-3-chloro-5-(trifluoromethyl)-2-pyridinone

Conditions	Yield
With potassium carbonate In water; dimethyl sulfoxide

1-[3-chloro-5-(3,3-dichloroallyloxy)-2-methoxyphenyl]ethanone O-(2-hydroxyethyl)-oxime (918311-09-8) + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → 1-[3-chloro-5-(3,3-dichloroallyloxy)-2-methoxyphenyl]ethanone O-[2-(3-chloro-5-trifluoromethylpyridin-2-yloxy)ethyl]oxime (918311-11-2)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; Mitsunobu reaction;

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → (RS,SR)-8-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-2,2-dimethyl-4-[1,2,4]triazol-1-yloctan-3-ol

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / potassium iodide / N,N-dimethyl-formamide / 0.5 h / 180 °C / microwave irradiation 2.1: titanium tetrachloride / dichloromethane / 0.5 h / -30 °C 2.2: 14 h / -30 - 20 °C View Scheme

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → (RR,SS)-8-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-2,2-dimethyl-4-[1,2,4]triazol-1-yloctan-3-ol

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / potassium iodide / N,N-dimethyl-formamide / 0.5 h / 180 °C / microwave irradiation 2: sodium tetrahydroborate; methanol / 14 h / 0 - 20 °C View Scheme

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) + methyl (E)-2-[2-(bromomethyl)phenyl]-2-(methoxyimino)acetate (133409-72-0) → (E)-2-(2-(((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)methyl)phenyl)-2-(methoxyimino)-N-methylacetamide

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / butanone / 0.5 h 1.2: 5 h / 80 °C 2.1: methanol / 3 h / 20 °C View Scheme

methyl (1s,4s)-4-hydroxy-2'-oxo-1',2'-dihydrospiro[cyclohexane-1,3'-indole]-5'-carboxylate + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → (1r,4r)-4-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)-2'-oxo-1',2'-dihydrospiro[cyclohexane-1,3'-indole]-5'-carboxylic acid

Conditions	Yield
Stage #1: methyl (1s,4s)-4-hydroxy-2'-oxo-1',2'-dihydrospiro[cyclohexane-1,3'-indole]-5'-carboxylate; 3-chloro-5-(trifluoromethyl)-2-hydroxypyridine With di-isopropyl azodicarboxylate In toluene at 80℃; for 3h; Stage #2: With water; sodium hydroxide In tetrahydrofuran; methanol at 50℃; for 3h;	12.1 mg

methyl (1r,4r)-4-hydroxy-2'-oxo-1',2'-dihydrospiro[cyclohexane-1,3'-pyrrolo[3,2-b]pyridine]-5'-carboxylate + 3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → C20H17ClF3N3O4

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In toluene at 10 - 35℃; for 16h;

3-chloro-2-hydroxy-5-(trifluoromethyl)pyridine (76041-71-9) → 3-chloro-4-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)aniline (76471-06-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 4 h / 100 °C 2: ammonium chloride; iron / ethanol; water / 6 h / Reflux View Scheme

Upstream product

• 69045-84-7 2,3-dichloro-5-trifluoromethylpyridine 
• 69045-83-6 2,3-dichloro-5-(trichloromethyl)pyridine 
• 5006-66-6 6-hydroxy-3-pyridinecarboxylic acid 
• 33252-63-0 2-hydroxy-5-(trifluoromethyl)pyridine 

Downstream Products

• 548766-54-7 methyl-phenyl-carbamic acid 3-chloro-5-trifluoromethyl-pyridin-2-yl ester 
• 918311-11-2 1-[3-chloro-5-(3,3-dichloroallyloxy)-2-methoxyphenyl]ethanone O-[2-(3-chloro-5-trifluoromethylpyridin-2-yloxy)ethyl]oxime 
• 1174281-15-2 3-chloro-5-(trifluoromethyl)-2-pyridinyl tosylate 
• 1613033-18-3 3-chloro-1-(3-(diethoxymethyl)phenyl)-5-(trifluoromethyl)-2(1H)-pyridinone 
• 75806-84-7 2-bromo-3-chloro-5-(trifluoromethyl)pyridine 
• 76471-06-2 3-chloro-4-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)aniline 
• 727375-79-3 3-chloro-1-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-5-trifluoromethyl-1H-pyridin-2-one 

Relevant academic research and scientific papers

A for the synthesis of anti-cancer auxiliary drug pyridine medical process for the preparation of intermediates

The invention relates to the field of medical chemistry and discloses a method for synthesizing a pyridine medical intermediate, namely 2-bromo-3-chloro-5-trifluoromethyl pyridine, for synthesizing anti-cancer auxiliary medicines. The method comprises the following steps of: (1) reacting 6-hydroxynicotinic acid, hydrofluoric acid and sulfur tetrafluoride at the temperature of between 100 and 120DEG C and under the pressure of 0.1-0.3MPa, and adding water to obtain 2-hydroxy-5-trifluoromethyl pyridine; (2) reacting with N-chlorosuccinimide, and performing water precipitation to obtain 3-chloro-5-trifluoromethyl-2-hydroxypyridine; and (3) adding excessive phosphorus oxybromide, reacting at the temperature of between 145 and 160DEG C for 5 to 8 hours, cooling, violently stirring at the temperature of between -5 and 0DEG C, extracting, combining organic phases, drying, filtering, performing spin drying, and purifying by using a silica gel column. According to the method, raw materials are readily available, the cost is low, the method is suitable for industrial production and the yield exceeds 38 percent.

SOME NEW 2-SUBSTITUTED 5-TRIFLUOROMETHYLPYRIDINES

The preparation of the derivatives of 2-amino-, hydrazino-, hydroxy-, and mercapto-5-trifluoromethylpyridines via 2-chloro precursors is describes.Experimental and spectral data of the products together with those of the precursors are presented.