Home Cart 0 Sign in  
X

[ CAS No. 69045-84-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 69045-84-7
Chemical Structure| 69045-84-7
Chemical Structure| 69045-84-7
Structure of 69045-84-7 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 69045-84-7 ]

Related Doc. of [ 69045-84-7 ]

Alternatived Products of [ 69045-84-7 ]
Product Citations

Product Details of [ 69045-84-7 ]

CAS No. :69045-84-7 MDL No. :MFCD00042243
Formula : C6H2Cl2F3N Boiling Point : -
Linear Structure Formula :- InChI Key :ABNQGNFVSFKJGI-UHFFFAOYSA-N
M.W : 215.99 Pubchem ID :112234
Synonyms :

Calculated chemistry of [ 69045-84-7 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.17
Num. rotatable bonds : 1
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 39.26
TPSA : 12.89 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.25 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.97
Log Po/w (XLOGP3) : 3.33
Log Po/w (WLOGP) : 4.56
Log Po/w (MLOGP) : 2.75
Log Po/w (SILICOS-IT) : 3.68
Consensus Log Po/w : 3.26

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.58
Solubility : 0.0567 mg/ml ; 0.000262 mol/l
Class : Soluble
Log S (Ali) : -3.28
Solubility : 0.114 mg/ml ; 0.000528 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.15
Solubility : 0.0153 mg/ml ; 0.0000708 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.99

Safety of [ 69045-84-7 ]

Signal Word:Danger Class:9
Precautionary Statements:P501-P261-P273-P272-P270-P210-P271-P264-P280-P302+P352-P370+P378-P391-P362+P364-P333+P313-P301+P312+P330-P304+P340+P312-P305+P351+P338+P310-P403+P235 UN#:3082
Hazard Statements:H227-H302+H332-H317-H318-H411 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 69045-84-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 69045-84-7 ]
  • Downstream synthetic route of [ 69045-84-7 ]

[ 69045-84-7 ] Synthesis Path-Upstream   1~27

  • 1
  • [ 69045-84-7 ]
  • [ 85148-26-1 ]
YieldReaction ConditionsOperation in experiment
7% With acetic acid; zinc In water at 90℃; for 1.25 h; Add zinc dust (1. 18 g) to a suspension of 2, 3-dichloro-5-trifluoromethyl-pyridine (2. 0 g, 9. 30 mmol) in 80 : 20 water and acetic acid (5 mL) and stir at 90 °C for 1 h. Add more zinc dust (1 g) and stir at 90 °C for an additional 15 min. Cool the reaction mixture to room temperature, filter, and wash with dichloromethane. Carefully concentrate and purify the residue by silica gel chromatography, eluting with 100 : 0 to 0 : 100 hexane : dichloromethane, to obtain the title compound as a volatile oil (0. 120g, 7percent). 1H NMR (300 MHz, CDCl3) 8 7. 93 (s, 1 H), 8. 78 (s, 2 H). GC-MS (EI) m/z = 181. 0, 183. 0 [M].
Reference: [1] Patent: WO2005/94822, 2005, A1, . Location in patent: Page/Page column 28
[2] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 20, p. 7150 - 7163
  • 2
  • [ 69045-84-7 ]
  • [ 89402-42-6 ]
YieldReaction ConditionsOperation in experiment
47.6% With potassium carbonate; cesium fluoride In dimethyl sulfoxide at 80 - 110℃; for 48 h; Inert atmosphere 1500 ml of DMSO, 363 g of cesium fluoride and 8 g of potassium carbonate were added to a 5000 ml reaction flask, heated in an oil bath, and depressurizedDMSO 600ml was concentrated and cooled to below 80°C. Under nitrogen protection, 318g (1.58 mol) of 2,3-dichloro-5-trifluoromethylpyridine was added and reacted at about 110°C for 48 hours. The yellow liquid was added with 600 ml of water, and the liquid was separated. The organic phase was dried over anhydrous magnesium sulfate. The crude product was filtered to obtain 188 g. Distillation yielded 139 g of a 100-102° C. fraction, which was 2,3-difluoro-5-trifluoromethylpyridine. The yield was 47.6percent.
40% With potassium carbonate; cesium fluoride In 1-methyl-pyrrolidin-2-one at 110 - 120℃; for 15 - 24 h; EXAMPLE 3; 2,3-difluoro-5-trifluoromethylpyridine (12-2); Equipment:; 2.5 l four-necked round bottom flask equipped with a thermometer, a mechanical stirrer a dropping funnel and an inert gas supply150 ml N-methyl-2-pyrrolidinone was evaporated at 110° C. and 25-30 mbar from a suspension of 2 l N-methyl-2-pyrrolidinone, 28 g potassium carbonate (202.6 mmol), and 615.0 g cesium fluoride (4.0 mol). The reaction mixture was treated with 170.0 g 2,3-dichloro-5-trifluoromethylpyridine (12-1, 779.2 mmol) and stirred at 120° C. for 24 h.The product 12-2 was directly distilled out of the reaction suspension at 95 to 110° C. and 40-50 mbar yielding 190 g of 12-2 as a mixture. 190 g of this mixture were extracted with 200 ml pentane and 400 ml water. After separation of the phases, the water phase was extracted with 2 l pentane. The combined pentane phase was distilled on a Sulzer-column at 40 to 100° C. yielding 60.0 g (40.4percent) of 12-2.GC analysis: 99.9 area-percent of 12-2; 4. Optimized Procedure to Difluoro Trifluoromethyl Pyridine (12-2); The synthesis of the 12-2 was elaborated starting from the corresponding dichloro compound 12-1 or from the very expensive chloro-fluoro compound 12-3. The reactivity of the chloro atom in the 2-position of 12-1 is significant higher compared with the chloro atom in the 3-position. Based on the known safety issue of DMSO in combination with bases like K2CO3 at high temperatures like 120° C., DMSO was substituted by N-methylpyrrolidinone (NMP). The heterogenic reaction is very water-sensitive. Traces of water led to longer reaction time and/or incomplete conversion. Longer reaction time (more than 17 h at 120° C.) or higher temperature led, due to the instability of the product 12-2, to several unknown by-products, ending up as a black tar in the reaction vessel. Therefore, it was necessary to work with water free solvent. A substantial amount of CsF was needed for this reaction. CsF is very hygroscopic and contaminated the reaction mixture with water. Therefore, to completely eliminate water from the reaction mixture, a defined amount of NMP was evaporated prior to the addition of dichloro compound 12-1 to the suspension of K2CO3 and CsF in NMP.
Reference: [1] Patent: CN104628679, 2018, B, . Location in patent: Paragraph 0061; 0064; 0065
[2] Patent: US2008/221327, 2008, A1, . Location in patent: Page/Page column 6; 9
  • 3
  • [ 69045-83-6 ]
  • [ 69045-84-7 ]
YieldReaction ConditionsOperation in experiment
92% at 170 - 180℃; for 5 h; Autoclave 26.5 g 0.1 mol 2,3-dichloro-5-trichloromethylpyridine,0.2 g of tungsten hexachlor into the reactor,Heated to 170 ° C at atmospheric pressure,And then hydrogen fluoride (about 20 g)The reaction is terminated when the test product is no longer changed,Unreacted hydrogen fluoride,After condensing recovery,The generated hydrogen chloride can be absorbed and removed.The reaction solution was cooled to room temperature,Transferred to an autoclave,Heated to 180 ° C,Pressure 0.2MPa,Reaction 5h,Cooling down,Sampling analysis,Containing 2,3-dichloro-5-trifluoromethylpyridine 94percentYield 92percent.
73% at 130 - 175℃; Autoclave EXAMPLE 3 Conversion of 2,3-dichloro-5-(trichloromethyl)pyridine to 2,3-dichloro-5- (trifluoromethyl)pyridine. 2,3-dichloro-5-(trichloromethyl)pyridine (5 g, 18.84 mmole), iron(III) chloride (0.153 g, 0.942 mmole) and hydrogen fluoride (2.423 g, 85 mmole) in pyridine solution (70percent) was added to an autoclave and heated to 175 °C over night. The autoclave was cooled to 130 °C and left for stirring additional 5 hours, followed by cooling to 25 °C and opened carefully leaving gas phase through a Caustic Lye scrubber. The crude was dissolved in dichloromethane, washed with 1 M NaOH (aq) and water. The organic phase was removed by distillation and the product was obtained by distillation (3.0 g, 73 percent yield).
63.2% at 70 - 200℃; for 30 h; 500 g (3.08 mol) of 2-chloro-5-chloromethylpyridine (molecular weight: 162 g / mol) and 50 g (10percent by weight) of copper oxide were charged into a 1 L four-necked flask equipped with a thermometer, a condenser and a mechanical stir And heated to 275 ° C, and then chlorinated by passing Cl 2 into the above solution, and the reaction was carried out for 60 hours to obtain 562 g (2.12 mol) of 2,3-dichloro-5-trichloromethylpyridine. A solution of 562 g (2.12 mol) of 2,3-dichloro-5-trichloromethylpyridine was heated to 70 ° C and added with 5 g of catalyst antimony pentachloride followed by 210 g (10.5 mol) of hydrogen fluoride at 200 ° C, 8.5 MPa pressure for 30 hours to give 421 g (1.95 mol) of 2,3-dichloro-5-trifluoromethylpyridine in a yield of 63.2percent from 2-chloro-5-chloromethylpyridine,
Reference: [1] Patent: CN106397309, 2017, A, . Location in patent: Paragraph 0023; 0024; 0025; 0025; 0026-0030
[2] Heterocycles, 1984, vol. 22, # 1, p. 117 - 124
[3] Patent: WO2014/198278, 2014, A1, . Location in patent: Page/Page column 8; 9; 12
[4] Patent: CN104557683, 2016, B, . Location in patent: Paragraph 0021; 0022
[5] Patent: US4590279, 1986, A,
[6] Patent: US4317913, 1982, A,
[7] Patent: CN106748985, 2017, A, . Location in patent: Paragraph 0030; 0032; 0033; 0036
  • 4
  • [ 52334-81-3 ]
  • [ 69045-84-7 ]
Reference: [1] Patent: US4420618, 1983, A,
[2] Patent: US4420618, 1983, A,
[3] Patent: US4420618, 1983, A,
  • 5
  • [ 7440-02-0 ]
  • [ 72537-17-8 ]
  • [ 69045-84-7 ]
Reference: [1] Patent: US4546192, 1985, A,
  • 6
  • [ 82107-24-2 ]
  • [ 107-13-1 ]
  • [ 69045-84-7 ]
Reference: [1] Tetrahedron, 1985, vol. 41, # 19, p. 4057 - 4078
  • 7
  • [ 72537-17-8 ]
  • [ 69045-84-7 ]
Reference: [1] Patent: US4546192, 1985, A,
  • 8
  • [ 7783-56-4 ]
  • [ 69045-83-6 ]
  • [ 69045-84-7 ]
Reference: [1] Patent: US4317913, 1982, A,
  • 9
  • [ 52334-81-3 ]
  • [ 13283-01-7 ]
  • [ 69045-84-7 ]
Reference: [1] Patent: US4420618, 1983, A,
  • 10
  • [ 59-67-6 ]
  • [ 69045-84-7 ]
Reference: [1] Patent: WO2014/198278, 2014, A1,
[2] Patent: WO2014/198278, 2014, A1,
[3] Patent: WO2014/198278, 2014, A1,
[4] Patent: WO2014/198278, 2014, A1,
[5] Patent: WO2014/198278, 2014, A1,
[6] Patent: WO2014/198278, 2014, A1,
[7] Patent: WO2014/198278, 2014, A1,
[8] Patent: WO2014/198278, 2014, A1,
[9] Patent: WO2014/198278, 2014, A1,
[10] Patent: WO2014/198278, 2014, A1,
[11] Patent: WO2014/198278, 2014, A1,
[12] Patent: WO2014/198278, 2014, A1,
[13] Patent: WO2014/198278, 2014, A1,
  • 11
  • [ 3099-50-1 ]
  • [ 69045-84-7 ]
Reference: [1] Patent: WO2014/198278, 2014, A1,
[2] Patent: WO2014/198278, 2014, A1,
  • 12
  • [ 108-99-6 ]
  • [ 69045-84-7 ]
Reference: [1] Patent: CN106748985, 2017, A,
  • 13
  • [ 69045-78-9 ]
  • [ 69045-84-7 ]
Reference: [1] Patent: CN106748985, 2017, A,
  • 14
  • [ 69045-84-7 ]
  • [ 79456-26-1 ]
YieldReaction ConditionsOperation in experiment
90% With ammonia In water at 80℃; for 9 h; Autoclave EXAMPLE 11 Conversion of 2,3-dichloro-5-(trifluoromethyl)pyridine to Fluazinam. 2,3-dichloro-5-(trifluoromethyl)pyridine (26,75 g, 0.125 mole) and water (25 ml) was added to an autoclave. The autoclave was closed and liquid ammonia (45 g, 2,85 mole) was added from a pressure bottle. The autoclave was heated to 80°C for 9 hours at a pressure between 22 and 18 bar. The reaction was cooled to room temperature and the intermediate, 2-amino-3- chloro-5-(trifluoromethyl)pyridine was obtained by filtration, washing with water and drying (22 g, 90percent). The intermediate was dissolved in acetonitril (230 ml). The solution was cooled to 5 °C and KOH (s., 12 g, 0.22 mole) was added. A solution of 2,4-dichloro-3,5-dinitro-5-(trifluoromethyl)benzene (25 g, 0.08 mole) in acetonitrile (230 ml) was added over 15 minutes with continuous cooling. The temperature was raised to 25 °C for four hours followed by a a temperature increase and kept at 40 °C for two hours. The mixture was added to 1500 ml of water, neutralised to a pH around 4 with 4N HCl (aq) and extracted with isopropyl acetate (2 x 750 ml). The organic phase was evaporated to dryness to get crude Fluazinam (43 g, 70 percent yield, 60 percent purity). The Fluazinam can be further purified by recrystallisation.
Reference: [1] Patent: WO2014/198278, 2014, A1, . Location in patent: Page/Page column 9; 17
[2] Heterocycles, 1984, vol. 22, # 1, p. 117 - 124
[3] Patent: US4349681, 1982, A,
  • 15
  • [ 69045-84-7 ]
  • [ 79456-26-1 ]
Reference: [1] Patent: US4331670, 1982, A,
  • 16
  • [ 69045-84-7 ]
  • [ 76041-71-9 ]
Reference: [1] Heterocycles, 1984, vol. 22, # 1, p. 117 - 124
  • 17
  • [ 69045-84-7 ]
  • [ 89570-82-1 ]
YieldReaction ConditionsOperation in experiment
7.57 g With hydrazine hydrate In ethanol at 50℃; Cooling with ice To a solution of 2,3-dichloro-5-(trifluoromethyl)pyridine (6.8 g) in ethanol (50 mL) was added hydrazine hydrate (3.15 g) in an ice bath, and the mixture was stirred overnight at 50° C.
The mixture was allowed to be cooled to room temperature, and the solvent was evaporated under reduced pressure. The obtained residue was treated with IPE, and the precipitated solid was collected by filtration to give the title compound (7.57 g).
MS (APCI+): [M+H]+ 212.0
Reference: [1] Heterocycles, 1984, vol. 22, # 1, p. 117 - 124
[2] Organic and Biomolecular Chemistry, 2004, vol. 2, # 2, p. 246 - 256
[3] Patent: US5321002, 1994, A,
[4] Patent: US2015/266872, 2015, A1, . Location in patent: Paragraph 0685; 0686
[5] Letters in Drug Design and Discovery, 2016, vol. 13, # 4, p. 324 - 328
[6] Patent: CN105541706, 2016, A, . Location in patent: Paragraph 0021; 0023
[7] Molecules, 2018, vol. 23, # 9,
[8] Patent: WO2009/117421, 2009, A2, . Location in patent: Page/Page column 51
  • 18
  • [ 69045-84-7 ]
  • [ 72537-17-8 ]
YieldReaction ConditionsOperation in experiment
100% With potassium carbonate; cesium fluoride In dimethyl sulfoxide at 120℃; for 4 h; EXAMPLE 3b; Equipment:; 250 ml four-necked round bottom flask equipped with a thermometer, a mechanical stirrer a dropping funnel and an inert gas supply25 ml DMSO was evaporated at 120° C. and 25-30 mbar from a suspension of 150 ml DMSO, 2.5 g potassium carbonate (17.9 mmol) and 25.0 g cesium fluoride (162.9 mmol). The reaction mixture was treated with 25.0 g 2,3-dichloro-5-trifluoromethylpyridine (12-1, 112.3 mmol) and stirred at 120° C. for 4 h. The suspension was filtered and the product 12-3 was directly distilled out of the distillate at 95 to 115° C. and 40-60 mbar to get 12-3 in quantitative yield. GC analysis: 96.9 area-percent of 12-3.
98% With potassium carbonate; cesium fluoride In 1-methyl-pyrrolidin-2-one at 70℃; for 1 - 3 h; 4. Optimized Procedure to Difluoro Trifluoromethyl Pyridine (12-2); The synthesis of the 12-2 was elaborated starting from the corresponding dichloro compound 12-1 or from the very expensive chloro-fluoro compound 12-3. The reactivity of the chloro atom in the 2-position of 12-1 is significant higher compared with the chloro atom in the 3-position. Based on the known safety issue of DMSO in combination with bases like K2CO3 at high temperatures like 120° C., DMSO was substituted by N-methylpyrrolidinone (NMP). The heterogenic reaction is very water-sensitive. Traces of water led to longer reaction time and/or incomplete conversion. Longer reaction time (more than 17 h at 120° C.) or higher temperature led, due to the instability of the product 12-2, to several unknown by-products, ending up as a black tar in the reaction vessel. Therefore, it was necessary to work with water free solvent. A substantial amount of CsF was needed for this reaction. CsF is very hygroscopic and contaminated the reaction mixture with water. Therefore, to completely eliminate water from the reaction mixture, a defined amount of NMP was evaporated prior to the addition of dichloro compound 12-1 to the suspension of K2CO3 and CsF in NMP.
97% With potassium fluoride; N-benzyl-N,N,N-triethylammonium chloride In N,N-dimethyl acetamide at 170℃; for 5 h; 500mL glass bottle,Supporting serpentine condenser,54.0 g (0.25 mol) of 2,3-dichloro-5-trifluoromethylpyridine,DMAC 150g,Anhydrous KF 18.9 g (0.325 mol),4 g (0.018 mol) of benzyltriethylammonium chloride,The temperature of the oil bath was raised to 170 ° C,Time reaction 5h,After DMAC was recovered by distillation,2-Fluoro-3-chloro-5-trifluoromethylpyridine was collected under reduced pressure48.6g,Its content of 2-fluoro-3-chloro-5-trifluoromethylpyridine was 99.5percentYield 97percent.
93.6% With potassium fluoride In dimethyl sulfoxide at 115 - 120℃; Inert atmosphere Under a nitrogen atmosphere, a 2 L four-necked round bottom flask was charged with 178.7 g (0.827 mol) of2,3-dichloro-5-trifluoromethylpyridine, 57.6 g (0.992 mol) of anhydrous KFAnd 200 mL of DMSO, The resulting mixture is heated to 115 ° C to 120 ° C and incubated for 3 to 5 hours, cooled to room temperature.Filtered and washed with 40 mL of DMSO to give a DMSO solution of 2-fluoro-3-chloro-5-trifluoromethylpyridine. The fractions were collected by distillation under reduced pressure at 50-55C / 11 mmHg to give a colorless liquid2-Fluoro-3-chloro-5-trifluoromethylpyridine, GC purity of 98.3percent, the yield of 93.6percent.
89.2% With potassium carbonate; cesium fluoride In dimethyl sulfoxide at 120℃; for 4 h; Inert atmosphere The 1500ml DMSO, 250g 25g of potassium carbonate and cesium fluoride were added to a 5000ml reaction flask was heated in an oil bath, concentrated under reduced pressure to a 500ml DMSO; under nitrogen, was added 250g2,3--dichloro-5-trifluoromethylpyridine, The reaction at 120 4 hours; distillation under reduced pressure to give a colorless liquid 206g, a yield of 89.2percent.

Reference: [1] Patent: US2008/221327, 2008, A1, . Location in patent: Page/Page column 9-10
[2] Patent: US2008/221327, 2008, A1, . Location in patent: Page/Page column 6
[3] Patent: CN107286087, 2017, A, . Location in patent: Paragraph 0032; 0033
[4] Patent: CN106905231, 2017, A, . Location in patent: Paragraph 0077; 0078; 0079; 0080; 0081; 0082; 0083-0085
[5] Patent: EP1199305, 2002, A1, . Location in patent: Page 6
[6] Patent: CN104628679, 2018, B, . Location in patent: Paragraph 0061-0063
  • 19
  • [ 67-56-1 ]
  • [ 69045-84-7 ]
  • [ 175136-17-1 ]
Reference: [1] Journal of Fluorine Chemistry, 1996, vol. 79, # 1, p. 9 - 12
  • 20
  • [ 74-90-8 ]
  • [ 69045-84-7 ]
  • [ 80194-70-3 ]
YieldReaction ConditionsOperation in experiment
85.7%
Stage #1: With triethylamine In methanol for 4 h; Reflux; Large scale
Stage #2: at 0℃; for 3 h; Large scale
1.82 kg of 3-chloro-2-chloro-5-trifluoromethylpyridine was dissolved in 27.231 L of methanol,Then 1.0119 kg of triethylamine was added thereto,Heated to reflux for 4 hours, and cooled to 20 ° C to obtain a reaction solution,The resulting reaction solution was filtered to obtain a filter cake,The resulting filter cake was vacuum dried at 40 ° C for 1 hour to obtain an organic salt; The organic salt obtained in step (1), 0.27 kg of hydrocyanic acid was added to 2.7 L of dichloromethane and 1.35 L of water,The reaction was stirred at 0 ° C for 3 hours to obtain a mixed solution, and the resulting mixture was allowed to stand at room temperature to obtain an organic phase a;The obtained organic phase a is added to hydrochloric acid to adjust its pH to 2 and then the layers are separated to obtain an acid water layer and an organic layer,The resulting organic layer was washed with water to a pH of 6 to give the washed water and the organic phase b; The organic phase b obtained in step is distilled at atmospheric pressure to 60 ° C and then distilled under reduced pressure,Collection of vacuum 2mmHg,The temperature of the ketone temperature of 70 to 120 ° C is 1.77 kg of 3-chloro-2-cyano-5-trifluoromethylpyridine,Yield 85.7percent.
Reference: [1] Patent: CN106349159, 2017, A, . Location in patent: Paragraph 0024
  • 21
  • [ 143-33-9 ]
  • [ 69045-84-7 ]
  • [ 80194-70-3 ]
YieldReaction ConditionsOperation in experiment
75.7%
Stage #1: With dmap In propiononitrileHeating / reflux
Stage #2: for 5 h;
2,3-dichloro-5-(trifluoromethyl)pyridine (5.65 mL, 40.5 mmol) was combined with 4-(dimethylamino)pyridine (5.20 g, 42.6 mmol) and propionitrile (65 mL), heated to reflux and agitated overnight. The mixture was cooled to ambient temperature and solution of sodium cyanide (3.00 g, 61.2 mmol) in water (11 mL) was added. After stirring for 5 hours, the reaction was diluted with water (25 mL) and organic phase was separated, washed with water and 2M HCl, dried and evaporated to give the product, 3-chloro-5- (trifluoromethyl)picolinonitrile (6.33 g, 75.7percent yield) as red liquid.
Reference: [1] Patent: WO2008/118718, 2008, A2, . Location in patent: Page/Page column 76
  • 22
  • [ 773837-37-9 ]
  • [ 69045-84-7 ]
  • [ 80194-70-3 ]
YieldReaction ConditionsOperation in experiment
73%
Stage #1: for 5 h; Heating / reflux
Stage #2: at 15℃; for 5 h;
Example 3
propionitrile (656 ml), 2,3-dichloro-5-trifluoromethylpyridine (87.5 g) and 4-dimethylaminopyridine (52 g) were heated at reflux for 5 hours under nitrogen..
The mixture was cooled and a solution of sodium cyanide (30 g) in water (110 ml) added at 15° C.
After stirring at 15° C. for 5 hours the reaction was complete and water (250 ml) added to dissolve the inorganic salts..
The organic phase was washed with water followed by extraction with 2N HCl to remove 4-dimethylaminopyridine..
propionitrile was removed by vacuum distillation at 40° C. to give the product, 3-chloro-2-cyano-5-trifluoromethylpyridine in 73 to 84percent yield.
Reference: [1] Patent: US6699993, 2004, B1, . Location in patent: Page column 4
[2] Patent: US6699993, 2004, B1, . Location in patent: Page column 3
[3] Patent: US6699993, 2004, B1, . Location in patent: Page column 3
[4] Patent: US6699993, 2004, B1, . Location in patent: Page column 3
[5] European Journal of Medicinal Chemistry, 2015, vol. 93, p. 101 - 108
  • 23
  • [ 69045-84-7 ]
  • [ 80194-70-3 ]
YieldReaction ConditionsOperation in experiment
91%
Stage #1: With dmap In acetone for 5 h; Reflux; Large scale
Stage #2: at 10℃; for 2 h; Large scale
2.16 kg of 2,3-dichloro-5-trifluoromethylpyridine was dissolved in 43.2 L of acetone,Then, an activator of 2.46 kg of 4-dimethylaminopyridine was added thereto, heated under reflux for 5 hours, cooled to 25 ° C,The resulting reaction solution was filtered and the resulting reaction solution was filtered to obtain a cake. The resulting cake was vacuum dried at 45 ° C for 1.5 hours to obtain an organic salt; The organic salt obtained in step (1), 0.716 kg of potassium cyanide was added to 8.60 L of dichloromethane and 1.72 L of water,The reaction was stirred at 10 ° C for 2 hours to obtain a mixed solution, and the resulting mixture was allowed to stand at room temperature to obtain an organic phase a;The organic phase a was added to hydrochloric acid to adjust its pH to 4 and then allowed to stand for delamination to obtain an acid water layer and an organic layer,The resulting organic layer was washed with water to a pH of 6 to give the washed water and the organic phase b; The organic phase b obtained in step was distilled at atmospheric pressure to 60 ° C and then distilled under reduced pressure to collect a vacuum of 2 mmHg. The temperature of the kettle temperature was 70-120 ° C was 3-chloro-2-cyano-5-trifluoromethylpyridine 1.88kg,Yield 91percent
Reference: [1] Patent: CN106349159, 2017, A, . Location in patent: Paragraph 0027
[2] Patent: US6699993, 2004, B1, . Location in patent: Page column 3
  • 24
  • [ 69045-84-7 ]
  • [ 80194-70-3 ]
Reference: [1] Patent: CN106905231, 2017, A,
  • 25
  • [ 10442-39-4 ]
  • [ 69045-84-7 ]
  • [ 80194-70-3 ]
Reference: [1] Patent: US6699993, 2004, B1, . Location in patent: Page column 3
  • 26
  • [ 69045-84-7 ]
  • [ 75806-84-7 ]
Reference: [1] Organic Letters, 2014, vol. 16, # 1, p. 110 - 113
  • 27
  • [ 69045-84-7 ]
  • [ 845614-11-1 ]
Reference: [1] Patent: CN104628679, 2018, B,
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 69045-84-7 ]

Fluorinated Building Blocks

Chemical Structure| 52334-81-3

[ 52334-81-3 ]

2-Chloro-5-trifluoromethylpyridine

Similarity: 0.85

Chemical Structure| 55304-75-1

[ 55304-75-1 ]

2,6-Dichloro-3-(trifluoromethyl)pyridine

Similarity: 0.78

Chemical Structure| 71701-96-7

[ 71701-96-7 ]

5-Chloro-2-fluoro-3-(trifluoromethyl)pyridine

Similarity: 0.74

Chemical Structure| 39890-98-7

[ 39890-98-7 ]

2,6-Dichloro-4-(trifluoromethyl)pyridine

Similarity: 0.73

Chemical Structure| 70158-59-7

[ 70158-59-7 ]

2,5-Dichloro-3-(trifluoromethyl)pyridine

Similarity: 0.72

Chlorides

Chemical Structure| 52334-81-3

[ 52334-81-3 ]

2-Chloro-5-trifluoromethylpyridine

Similarity: 0.85

Chemical Structure| 55304-75-1

[ 55304-75-1 ]

2,6-Dichloro-3-(trifluoromethyl)pyridine

Similarity: 0.78

Chemical Structure| 71701-96-7

[ 71701-96-7 ]

5-Chloro-2-fluoro-3-(trifluoromethyl)pyridine

Similarity: 0.74

Chemical Structure| 39890-98-7

[ 39890-98-7 ]

2,6-Dichloro-4-(trifluoromethyl)pyridine

Similarity: 0.73

Chemical Structure| 54127-30-9

[ 54127-30-9 ]

(5,6-Dichloropyridin-3-yl)methanol

Similarity: 0.73

Trifluoromethyls

Chemical Structure| 52334-81-3

[ 52334-81-3 ]

2-Chloro-5-trifluoromethylpyridine

Similarity: 0.85

Chemical Structure| 55304-75-1

[ 55304-75-1 ]

2,6-Dichloro-3-(trifluoromethyl)pyridine

Similarity: 0.78

Chemical Structure| 71701-96-7

[ 71701-96-7 ]

5-Chloro-2-fluoro-3-(trifluoromethyl)pyridine

Similarity: 0.74

Chemical Structure| 39890-98-7

[ 39890-98-7 ]

2,6-Dichloro-4-(trifluoromethyl)pyridine

Similarity: 0.73

Chemical Structure| 70158-59-7

[ 70158-59-7 ]

2,5-Dichloro-3-(trifluoromethyl)pyridine

Similarity: 0.72

Related Parent Nucleus of
[ 69045-84-7 ]

Pyridines

Chemical Structure| 52334-81-3

[ 52334-81-3 ]

2-Chloro-5-trifluoromethylpyridine

Similarity: 0.85

Chemical Structure| 55304-75-1

[ 55304-75-1 ]

2,6-Dichloro-3-(trifluoromethyl)pyridine

Similarity: 0.78

Chemical Structure| 71701-96-7

[ 71701-96-7 ]

5-Chloro-2-fluoro-3-(trifluoromethyl)pyridine

Similarity: 0.74

Chemical Structure| 39890-98-7

[ 39890-98-7 ]

2,6-Dichloro-4-(trifluoromethyl)pyridine

Similarity: 0.73

Chemical Structure| 54127-30-9

[ 54127-30-9 ]

(5,6-Dichloropyridin-3-yl)methanol

Similarity: 0.73