158063-66-2

Basic information

• Product Name: 4-(Trifluoromethyl)nicotinic acid
• Synonyms: 4-(Trifluoromethyl)pyridine-3-carboxylic acid, 3-Carboxy-4-(trifluoromethyl)pyridine;FlonicaMide Metabolite (TFNA type, 4-TriuoroMethyl nicotinic acid);4-(TrifluoroMethyl)-3-Pyridinecarboxylic Acid;3-Pyridinecarboxylic acid, 4-(trifluoromethyl)-;4-(Trifluoromethyl)pyridine-3-carboxylic acid 98%;4-(Trifluoromethyl)pyridine-3-carboxylic acid, >=98%;BUTTPARK 43\57-42;4-(TRIFLUOROMETHYL)NICOTINIC ACID
• CAS NO: 158063-66-2
• Molecular Formula: C₇H₄F₃NO₂
• Molecular Weight: 191.11
• EINECS: -0
• Product Categories: Building Blocks;C6 to C7;Chemical Synthesis;Heterocyclic Building Blocks;Fluorine series;Nitrogen cyclic compounds;Pyridine Series;Carboxylic Acids;Pyridines;Carboxylic Acids
• Mol File: 158063-66-2.mol
• Article Data: 17

Chemical Properties

• Melting Point: 146-148 °C(lit.)
• Boiling Point: 290.4 °C at 760 mmHg
• Flash Point: 129.4 °C
• Appearance: /
• Density: 1.484 g/cm³
• Vapor Pressure: 0.00858mmHg at 25°C
• Refractive Index: 1.517
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 2.50±0.36(Predicted)
• CAS DataBase Reference: 4-(Trifluoromethyl)nicotinic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(Trifluoromethyl)nicotinic acid(158063-66-2)
• EPA Substance Registry System: 4-(Trifluoromethyl)nicotinic acid(158063-66-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 158063-66-2(Hazardous Substances Data)

Usage

Uses

4-(Trifluoromethyl)-3-Pyridinecarboxylic Acid is a useful synthetic intermediate. It can be used to prepare pyridine carboxamides as palm site inhibitors of HCV NS5B polymerase. It can also be used to synthesize pyrazolylcarboxanilides as Ca2+ release-activated Ca2+ (CRAC) channel inhibitors.

Application

4-(Trifluoromethyl)nicotinic acid is a trifluoromethyl-containing aromatic compound with unique biological activity, which can be used as a precursor material for the preparation of other pesticides or medicines. 4-(Trifluoromethyl)nicotinic acid is a key intermediate of flonicamid, a highly effective insecticide.

Preparation

synthesis of 4-(Trifluoromethyl)nicotinic acid: add 5g (0.0192mol) Methyl 2,6-dichloro-4-(trifluoromethyl)nicotinate in turn to a 100mL three-necked flask, 0.3g of 10% Pd/C (water content 63.45%) ), 5.25g (0.0389mol) CH3COONa 3H2O and 20mL ethanol, after stirring and dissolving, nitrogen was replaced 3 times to discharge air, after hydrogen replacement 2 times, the reaction was stirred at room temperature for 8h under a hydrogen atmosphere until no hydrogen was absorbed to complete the reaction, and suction filtration was recovered. Palladium carbon, washed the filter cake 3 times with ethanol, the filtrate was rotary evaporated to remove the solvent, added 20 mL of water to the obtained solid, fully shaken to dissolve it, added hydrochloric acid to adjust pH=2～3, extracted 3 times with ethyl acetate, The organic phases were combined and washed three times with saturated brine, dried over anhydrous sodium sulfate, and rotary-evaporated to obtain 3.3 g of a pale yellow solid with a yield of 90.4%.

InChI:InChI=1/C7H3Cl2F3N2O/c8-3-1-2(7(10,11)12)4(6(13)15)5(9)14-3/h1H,(H2,13,15)

Synthetic route

4-trifluoromethyl-3-pyridinecarboxamide (158062-71-6) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
With sodium hydroxide In water at 100℃; for 4h; Concentration;	99.1%
Stage #1: 4-trifluoromethyl-3-pyridinecarboxamide With hydrogenchloride; water for 5h; Heating / reflux; Stage #2: With sodium carbonate In water pH=3;	89.7%
With sodium hydroxide at 100℃; for 5h;

4-(trifluoromethyl)nicotinonitrile (13600-43-6) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
With water; sodium hydroxide at 100℃; Temperature;	98.3%
With sodium hydroxide In ethanol at 80℃; for 10h; Temperature; Inert atmosphere;	90.1%
Stage #1: 4-(trifluoromethyl)nicotinonitrile With potassium hydroxide; water In water; ethylene glycol at 200℃; for 4h; Stage #2: With hydrogenchloride In water; ethylene glycol at 20℃;	84%
With sulfuric acid In water at 110℃; for 12h;

2-chloro-4-(trifluoromethyl)pyridine-3-carboxylic acid (590371-81-6) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
With ammonium formate; 10% palladium on active carbon In methanol at 25℃; for 0.25h;	89%

N-(2-methoxycarbonylvinyl)-4,4,4-trifluoro-3-one-1-butenamine → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
Stage #1: N-(2-methoxycarbonylvinyl)-4,4,4-trifluoro-3-oxo-1-butenamine With sodium methylate In methanol at 20 - 65℃; for 7h; Inert atmosphere; Stage #2: With water at 20℃; for 12h;	86.2%
Stage #1: N-(2-methoxycarbonylvinyl)-4,4,4-trifluoro-3-oxo-1-butenamine With sodium methylate In methanol for 6.5h; Reflux; Stage #2: With water; sodium hydroxide In methanol at 50℃; Time;	75%
With sodium methylate In methanol at 20℃; for 6.5h; Time; Reflux;

4-trifluoromethylpyridine (3796-24-5) + carbon dioxide (124-38-9) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
With 2,2,6,6-tetramethylpiperidinyl-lithium In tetrahydrofuran at -75℃; for 2h;	84%

carbon dioxide (124-38-9) + 3-iodo-4-(trifluoromethyl)pyridine (625115-02-8) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane at -75℃; for 0.0333333h;	81%

N-2-methoxycarbonylvinyl 4,4,4-trifluoro-3-oxo-1-butenylamine → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
With sodium hydroxide In methanol; diethyl ether; water	77%

dimethyl (methoxymethylene)malonate (22398-14-7) + 4-amino-1,1,1-trifluoro-3-butene-2-one (120417-45-0) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
Stage #1: 4-amino-1,1,1-trifluoro-3-butene-2-one With sodium hydride In 1-methyl-pyrrolidin-2-one at 0 - 10℃; for 1h; Stage #2: dimethyl (methoxymethylene)malonate In 1-methyl-pyrrolidin-2-one; methanol at 65℃; for 7h; Stage #3: With hydrogenchloride In 1-methyl-pyrrolidin-2-one; methanol; water for 9h; Reagent/catalyst; Solvent; Temperature; Reflux;	49%

3-methoxy-2-propenenitrile (60838-50-8) + 4-amino-1,1,1-trifluoro-3-butene-2-one (120417-45-0) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
Stage #1: 3-methoxy-2-propenenitrile; 4-amino-1,1,1-trifluoro-3-butene-2-one With sodium hydride In tetrahydrofuran at 0 - 20℃; for 3.33333h; Stage #2: With hydrogenchloride In tetrahydrofuran; water Stage #3: With hydrogenchloride; sodium hydroxide; water; sodium methylate more than 3 stages;	45.3%

4-trifluoromethylpyridine (3796-24-5) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 79 percent / 2,2,6,6-tetramethylpiperidine; butyllithium; iodine / tetrahydrofuran; hexane / 2 h / -75 °C 2: 81 percent / butyllithium / tetrahydrofuran; hexane / 0.03 h / -75 °C View Scheme

2-chloro-4-trifluoromethyl pyridine (81565-18-6) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / diisopropylamine; butyllithium / hexane; tetrahydrofuran / 2 h / -75 °C 2: 89 percent / ammonium formate / palladium (10 percent on charcoal) / methanol / 0.25 h / 25 °C View Scheme

2,6-dichloro-4-(trifluoromethyl)pyridine-3-carbonitrile (13600-42-5) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide; water / 8 h / 20 °C 2: hydrogen; triethylamine; 5%-palladium/activated carbon / methanol / Reflux View Scheme
Multi-step reaction with 2 steps 1: triethylamine; hydrogen; palladium on activated carbon / tetrahydrofuran / 4 h 2: sodium hydroxide / ethanol / 10 h / 80 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: sodium bromide; sulfuric acid 2: sodium carbonate; 5%-palladium/activated carbon; hydrogen / methanol / 6 h 3: sodium hydroxide / 5 h / 100 °C View Scheme

2,6-dichloro-4-trifluoromethylnicotinic acid (503437-19-2) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen; triethylamine In methanol Reagent/catalyst; Reflux;

2,6-dihydroxy-3-cyano-4-trifluoromethylpyridine N-methylmorpholine → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: trichlorophosphate / 18 h / 130 °C / Inert atmosphere 2: triethylamine; hydrogen; palladium on activated carbon / tetrahydrofuran / 4 h 3: sodium hydroxide / ethanol / 10 h / 80 °C / Inert atmosphere View Scheme

2,6-dihydroxy-3-cyano-4-(trifluoromethyl)pyridine (3335-46-4) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: trichlorophosphate / dichloromethane; N,N-dimethyl-formamide / 6 h / 125 °C 2: sodium bromide; sulfuric acid 3: sodium carbonate; 5%-palladium/activated carbon; hydrogen / methanol / 6 h 4: sodium hydroxide / 5 h / 100 °C View Scheme

2-aminoacetonitrile hydrochloride (6011-14-9) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → flonicamide

Conditions	Yield
Stage #1: 4-(trifluoromethyl)nicotinic acid With thionyl chloride In toluene at 0 - 120℃; for 2.5h; Inert atmosphere; Stage #2: 2-aminoacetonitrile hydrochloride With triethylamine In tetrahydrofuran; toluene at 0 - 25℃; for 10h; Inert atmosphere;	93.4%
With phosgene; triethylamine In toluene at -10 - 5℃; for 4h; Reagent/catalyst; Solvent; Temperature;	91.6%

N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → N-methoxy-N-methyl-4-(trifluoromethyl)nicotinamide (323180-94-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 5h; Inert atmosphere;	93%
With HATU; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 5h; Inert atmosphere;

cyanomethylamine sulfate (151-63-3) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → flonicamide

Conditions	Yield
With triethylamine In 1,2-dichloro-ethane at 0 - 35℃; for 4h; Solvent;	90.4%
With thionyl chloride; triethylamine; N-methyl-acetamide In tetrahydrofuran; benzene

4-(trifluoromethyl)nicotinic acid (158063-66-2) → 4-(trifluoromethyl)pyridine-3-carbonyl chloride (104326-73-0)

Conditions	Yield
With thionyl chloride; N,N-dimethyl-formamide In benzene for 3h; Heating / reflux;	90.1%
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 3h;
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h; Product distribution / selectivity;

4-(trifluoromethyl)nicotinic acid (158063-66-2) → 6-nitro-4-trifluoromethyl-3-picolinic acid

Conditions	Yield
With sulfuric acid; nitric acid at 0 - 20℃;	89.8%

1-t-Butoxycarbonylpiperazine (57260-71-6) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → tert-butyl 4-(4-(trifluoromethyl)nicotinoyl)piperazine-1-carboxylate

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 20h;	83.9%

C23H21N3O2S (1261276-98-5) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → C30H23F3N4O3S (1261275-82-4)

Conditions	Yield
Stage #1: 4-(trifluoromethyl)nicotinic acid With oxalyl dichloride; N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: C23H21N3O2S With pyridine In N,N-dimethyl-formamide at 20℃; for 0.0833333h;	82%

C17H22F3NO3 + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → C24H24F6N2O4

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 23℃;	82%

C18H22F3NO3 (1000894-58-5) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → C25H24F6N2O4

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane; N,N-dimethyl-formamide at 20℃; for 18h;	75%

2-aminoacetonitrile hydrochloride (6011-14-9) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → N-cyanomethyl-N,N-bis(4-trifluoromethylnicotinoyl)amine

Conditions	Yield
Stage #1: 2-aminoacetonitrile hydrochloride With triethylamine In 5,5-dimethyl-1,3-cyclohexadiene at 43℃; for 0.333333h; Stage #2: 4-(trifluoromethyl)nicotinic acid With oxalyl dichloride In 5,5-dimethyl-1,3-cyclohexadiene at -20 - 105℃; for 0.7h; Temperature;	73.7%

3-hydroxypiperazine (6859-99-0) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → C12H13F3N2O2 (1000894-22-3)

Conditions	Yield
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 20h;	70%

N,N-diethylhydrazine (616-40-0) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → N',N'-diethyl-4-(trifluoromethyl)nicotinohydrazide

Conditions	Yield
Stage #1: 4-(trifluoromethyl)nicotinic acid With triethylamine In dichloromethane at 20℃; for 0.0833333h; Stage #2: N,N-diethylhydrazine With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In tetrahydrofuran; dichloromethane at 20℃; for 0.5h;	64%

cycl-isopropylidene malonate (2033-24-1) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → C8H6F3NO (955997-27-0)

Conditions	Yield
With PyBOP; triethylamine In tetrahydrofuran at 20℃; for 18h;	62%
Stage #1: 4-(trifluoromethyl)nicotinic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: cycl-isopropylidene malonate In tetrahydrofuran at 20℃; Stage #3: With hydrogenchloride In tetrahydrofuran; water for 18h; Heating / reflux;	62%

cycl-isopropylidene malonate (2033-24-1) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → methyl 4-trifluoromethylpyridine-3-carboxylate (175204-82-7)

Conditions	Yield
Stage #1: cycl-isopropylidene malonate; 4-(trifluoromethyl)nicotinic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine In tetrahydrofuran at 20℃; Stage #2: With hydrogenchloride; water In tetrahydrofuran for 18h; Stage #3: In tetrahydrofuran; water	62%

5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → 5-[4-[[4-(trifluoromethyl)pyridin-3-yl]carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione

Conditions	Yield
With pyridine Heating;	60%

4-(trifluoromethyl)nicotinic acid (158063-66-2) + methyl iodide (74-88-4) → methyl 4-trifluoromethylpyridine-3-carboxylate (175204-82-7)

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 12h;	56.1%
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 12h;	56.1%

1,7,11-trideacetyl-pyripyropene A + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → 1,7,11-tri-deacetyl-1,7,11-tri-O-(4-trifluoromethyl-3-pyridylcarbonyl)pyripyropene A (1351304-15-8)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 68h;	56%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 17.5h;	36 mg

serinol (534-03-2) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → N-(4-trifluoromethylnicotinoyl)serinol (506433-31-4)

Conditions	Yield
Stage #1: 4-(trifluoromethyl)nicotinic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 40 - 50℃; for 6h; Stage #2: serinol In tetrahydrofuran at 50 - 60℃; for 4h;	55.3%

2-amino-1-(4-chlorophenyl)-3-methylbutan-1-one hydrochloride (1407542-08-8) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → N-(1-(4-chlorophenyl)-3-methyl-1-oxobutan-2-yl)-4-(trifluoromethyl)nicotinamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 30℃; for 16h;	51%

4-(4,5-dimethyl-6-(4-(methylamino)piperidin-1-yl)pyridazin-3-yl)benzonitrile (1227070-29-2) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → N-(1-(6-(4-cyanophenyl)-4,5-dimethylpyridazin-3-yl)piperidin-4-yl)-N-methyl-4-(trifluoromethyl)nicotinamide hydrochloride (1227070-13-4)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane for 72h;	49%

1,7,11-tri-deacetyl-1,11-di-O-propionylpyripyropene A (915971-55-0) + 4-(trifluoromethyl)nicotinic acid (158063-66-2) → 1,7,11-tri-deacetyl-1,11-di-O-propionyl-7-O-(4-trifluoromethyl-3-pyridylcarbonyl)pyripyropene A (915971-76-5)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 4.5h;	49%

Upstream product

• 3796-24-5 4-trifluoromethylpyridine 
• 124-38-9 carbon dioxide 
• 625115-02-8 3-iodo-4-(trifluoromethyl)pyridine 
• 81565-18-6 2-chloro-4-trifluoromethyl pyridine 
• 158062-71-6 4-trifluoromethyl-3-pyridinecarboxamide 
• 13600-43-6 4-(trifluoromethyl)nicotinonitrile 
• 22398-14-7 dimethyl (methoxymethylene)malonate 
• 120417-45-0 4-amino-1,1,1-trifluoro-3-butene-2-one 
• 3335-46-4 2,6-dihydroxy-3-cyano-4-(trifluoromethyl)pyridine 
• 503437-19-2 2,6-dichloro-4-trifluoromethylnicotinic acid 
• 13600-42-5 2,6-dichloro-4-(trifluoromethyl)pyridine-3-carbonitrile 
• 60838-50-8 3-methoxy-2-propenenitrile 
• 590371-81-6 2-chloro-4-(trifluoromethyl)pyridine-3-carboxylic acid 

Downstream Products

• 104326-73-0 4-(trifluoromethyl)pyridine-3-carbonyl chloride 
• 955997-27-0 C₈H₆F₃NO 
• 198401-76-2 (4-(trifluoromethyl)pyridin-3-yl)methanol 
• 1203486-92-3 methyl 2-amino-3-(4-(trifluoromethyl)nicotinamido)benzoate 
• 55279-30-6 methyl 3-aminoisonicotinate 
• 7579-20-6 3-Aminopyridine-4-carboxylic acid 
• 175204-80-5 4-(trifluoromethyl)pyridin-3-amine 
• 782431-54-3 3-chloromethyl-4-trifluoromethylpyridine 
• 1571136-23-6 C₂₄H₂₂F₆N₂O₄ 
• 1571136-24-7 C₂₃H₂₀F₆N₂O₄ 
• 1571136-22-5 C₃₅H₃₈F₆N₄O₆ 
• 1601475-78-8 C₃₇H₃₄F₆N₄O₄ 

Relevant articles and documents

Method for preparing 4-trifluoromethyl nicotinic acid

The invention belongs to the technical field of synthesis of pesticide intermediates, particularly relates to a method for preparing 4-trifluoromethyl nicotinic acid, and solves the problems that a preparation method of 4-trifluoromethyl nicotinic acid in the prior art is high in toxicity, heavy in pollution, not suitable for industrial production or tedious in steps. The method comprises the following steps: in a solvent, under the action of alkali, taking N-(2-methoxycarbonyl vinyl)-4, 4, 4-trifluoro-3-one-1-buteneamine as a raw material, and carrying out cyclization and hydrolysis reaction to prepare the target product 4-trifluoromethyl nicotinic acid by a one-step method. The preparation method is simple and convenient to operate, mild in reaction condition and relatively environment-friendly in preparation process, and the obtained 4-trifluoromethyl nicotinic acid product is high in purity, good in quality and suitable for industrial mass production.

Preparation method of 4-trifluoromethyl nicotinic acid

The invention relates to a synthetic method of 4-trifluoromethyl nicotinic acid. The method is characterized by comprising the following steps: (1) in a solvent A, enabling methyl acrylate to react for 30-60 minutes at 25-90 DEG C under the action of a catalyst and an oxidizing agent, with the molar ratio of methyl acrylate to the catalyst to the oxidizing agent being 1:(0.01-0.05):(1-1.5), so asto prepare methyl 3-oxopropionate; (2) in a solvent B, controlling the mole ratio of the methyl 3-oxopropionate to 4-amino-1,1,1-trifluoro-3-buten-2-one to be (1-1.5):1, reacting at 25-90 DEG C for 30-60 min to prepare N-(2-methoxycarbonyl vinyl)-4,4,4-trifluoro-3-one-1-butenylamine, then adding an alkali, with the mole ratio of the N-(2-methoxycarbonyl vinyl)-4,4,4-trifluoro-3-one-1-butenylamineto the alkali being 1:1-5, performing ring closing hydrolysis at 25-90 DEG C under the action of the alkali for 30-60 min, subjecting the reaction product to rectification separation after the reaction is finished to obtain a 4-trifluoromethyl nicotinic acid finished product. The method has the advantages that the adopted raw materials are cheap and easy to obtain, the synthesis method is simple to operate, reaction conditions are mild, requirements on equipment are low, and the method is suitable for industrial large-scale production.

Method for preparing 4-(trifluoromethyl)nicotinic acid

The invention discloses a method for preparing 4-(trifluoromethyl)nicotinic acid, and belongs to the technical field of methods for preparing chemical pharmaceutical intermediates. The method comprises steps of using trifluoroacetyl chloride, vinyl ethyl ether and 3-aminoacrylonitrile as raw materials to prepare the 4-(trifluoromethyl)nicotinic acid through acylation, cyclization and hydrolysis reactions. The method provided by the invention is relatively cheap and easily available in adopted raw material, simple and convenient to operate, easy in separation and purification of products in each step, high in yield, and more suitable for industrial production.