348-59-4|2,5-Dichlorofluorobenzene| Ambeed

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Quality Control of [ 348-59-4 ] Purity: 98% SDS Specification

COA

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NMR

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Product Details of [ 348-59-4 ]

CAS No. :	348-59-4
Formula :	C₆H₃Cl₂F
M.W :	164.99
SMILES Code :	FC1=C(Cl)C=CC(Cl)=C1
MDL No. :	MFCD00060656
InChI Key :	BJQTYCQGIXZSNM-UHFFFAOYSA-N
Pubchem ID :	136173

Safety of [ 348-59-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H227-H315-H319
Precautionary Statements:	P210-P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313-P403+P235-P501

Computational Chemistry of [ 348-59-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	36.42
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	0.0 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.14
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.37
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.55
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	3.91
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	3.57
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.31

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.48
Solubility	0.0547 mg/ml ; 0.000332 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.05
Solubility	0.148 mg/ml ; 0.000895 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.9
Solubility	0.0208 mg/ml ; 0.000126 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	Low
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-4.91 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	2.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.67

Application In Synthesis of [ 348-59-4 ]

* 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.

Downstream synthetic route of [ 348-59-4 ]

[ 348-59-4 ] Synthesis Path-Downstream 1~35

1
[ 95-82-9 ]
[ 348-59-4 ]

Yield	Reaction Conditions	Operation in experiment
95%		General procedure: 14 Typical continuous diazotization procedure: Material A (50 mL of aqueous solution containing amine (100 mmol), fluoroboric acid (120 mmol), hydrochloric acid (180 mmol)), and material B (50 mL of aqueous solution containing sodium nitrite (105 mmol)) were pumped into the T-joint at 4 mL/min, respectively, after a residence time of about 15 s at 25 C in a reacting tube, the mixture flowed through the outlet and accumulated in the cooling vessel. Vigorous stirring was maintained. The solid was filtered with suction after the slurry was cooled to -5 C. The solid was washed with methanol and then dried in vacuo to yield the corresponding diazonium tetrafluoroborate. 15 Typical continuous fluorodediazoniation procedure: Slurry of the diazonium tetrafluoroborate prepared as above in 300 mL of cosolvent was introduced into a reacting tube continuously at a flow rate of 4 mL/min. The mixture was maintained for 1 min at setting temperature and then cooled in the tandem tube. The collected liquid was washed with aqueous NaOH and water, nearly colorless liquid was obtained.

References: [1]Tetrahedron Letters,2013,vol. 54,p. 1261 - 1263.
[2]Journal of the American Chemical Society,1959,vol. 81,p. 94,95, 97.

2
[ 348-59-4 ]
[ 124-41-4 ]
[ 583-78-8 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 1063.

3
[ 348-59-4 ]
[ 124-41-4 ]
[ 583-78-8 ]
[ 1984-58-3 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1931,vol. 50,p. 753,779.

4
[ 348-59-4 ]
[ 583-78-8 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1931,vol. 50,p. 753,779.
[2]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 1063.

5
[ 348-59-4 ]
[ 2624-66-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sulfuric acid; nitric acid; at 0 - 20℃; for 4.16667h;	To a solution of 1,4- dichloro-2-fluorobenzene (2.227 g, 13.5 mmol) in sulfuric acid (3.59 mL, 67.3 mmol) at 0C was added nitric acid (0.612 mL, 13.50 mmol) dropwise over 10 min. The reaction was stirred at rt for 4 h. The mixture was poured into ice water, extracted with EtOAc (150 mL). The extract was washed with water, saturated NaHCO3 solution and brine sequentially, dried over MgSO4, filtered and concentrated under vacuum. The residue was purified with a silica gel flash column, eluting with 0-20% EtOAc in hexane to afford 1,4- dichloro-2-fluoro-5-nitrobenzene (2.79 g, 13.29 mmol, 98 % yield) as a tan solid.1H NMR (CDCl3) d 7.40 (1H, d, J = 7.8 Hz), 8.09 (IH, d, J = 6.9 Hz).
1.3 g	With nitric acid; trifluoroacetic acid; at 20℃; for 3h;	(Step 1) Synthesis of 1,4-dichloro-2-fluoro-5-nitrobenzene (0422) According to (Step 1) of Example 19, <strong>[348-59-4]1,4-dichloro-2-fluorobenzene</strong> (1.00 g) was dissolved instead of 1-chloro-2-fluoro-4-methylbenzene in TFA (10 mL). To the solution, fuming nitric acid (5.0 mL) was added dropwise. The mixture was stirred at room temperature for 3 hours, and then, the solution was added to an aqueous sodium bicarbonate solution. The precipitated solid was collected by filtration and dried to obtain 1.30 g of the title compound as a white solid.
1.3 g	With nitric acid; trifluoroacetic acid; at 20℃; for 0.05h;	General procedure: 1-hloro-2-fluoro-4-methylbenzene (1.00 g) was dissolved in TFA (10 mL). The solution was cooled to 0C, and then, fuming nitric acid (5.0 mL) was added dropwise thereto. The mixture was stirred at 0C for 30 minutes, and then, the solution was added to an aqueous sodium bicarbonate solution and neutralized, followed by extraction with chloroform. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography (hexane/ethyl acetate) to obtain 1.31 g of the title compound as a white solid.

References: [1]Patent: WO2019/67702,2019,A1 .Location in patent: Page/Page column 389.
[2]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 9991 - 10000.
[3]Journal of the American Chemical Society,1959,vol. 81,p. 94,95, 97.
[4]Patent: US2017/217970,2017,A1 .Location in patent: Paragraph 0422.
[5]Patent: EP3590516,2020,A1 .Location in patent: Paragraph 0361; 0366.

6
[ 367-22-6 ]
[ 348-59-4 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 1063.

7
[ 106-46-7 ]
[ 352-33-0 ]
[ 696-02-6 ]
[ 348-59-4 ]
[ 22060-77-1 ]
[ 74298-18-3 ]

References: [1]Journal of Organic Chemistry,1980,vol. 45,p. 3597 - 3603.

8
[ 36556-50-0 ]
[ 1435-49-0 ]
[ 625-98-9 ]
[ 348-59-4 ]
[ 1435-48-9 ]

References: [1]Chemistry Letters,1987,p. 1589 - 1592.

9
[ 348-59-4 ]
[ 13656-50-3 ]

References: [1]Journal of general chemistry of the USSR,1967,vol. 37,p. 149 - 155.
Zhurnal Obshchei Khimii,1967,vol. 37,p. 163 - 170.

10
[ 13656-50-3 ]
[ 348-59-4 ]

References: [1]Journal of general chemistry of the USSR,1967,vol. 37,p. 149 - 155.
Zhurnal Obshchei Khimii,1967,vol. 37,p. 163 - 170.

11
[ 348-59-4 ]
[ 108-24-7 ]
[ 1894-96-8 ]

References: [1]Journal of general chemistry of the USSR,1962,vol. 32,p. 3078 - 3081.
Zhurnal Obshchei Khimii,1962,vol. 32,p. 3131 - 3134.

Yield	Reaction Conditions	Operation in experiment
92%	With trichloroisocyanuric acid; bromine; In tetrachloromethane; at -10 - 100℃; for 18h;Photolysis;	General procedure: Round bottom flask equipped with Dimroth condenser (chilled to -10 C) was charged with arenecarboxylic acid (1.8 mmol), chloroisocyanurate, brominating agent and solvent (8 mL). The mixture was magnetically stirred and heated in an oil bath under 3 W LED warm-white lamp irradiation (LL) or under fluorescent room light irradiation (FL). The cooled reaction mixture was filtered through a short silica gel pad, washed with 1 M aq Na2SO3, dried over Na2SO4, filtered and the solvent was removed by distillation. In case of volatile product the yield was determined by gas chromatography (GC) with internal standard. The results are presented in Table 7
		...presented by the following formula (4) which can respectively correspond to the formula (1) can be obtained. (D) Fluorine substituted aromatic compound represented by the formula (4) corresponding to the hydroxy compound wherein X1 is a substituent of the group (a) in the formula(1): ... 2,4-dinitrofluorobenzene, 2,5-dinitrofluorobenzene, 2,4,6-trinitrofluorobenzene, 2-cyanofluorobenzene, 3-cyanofluorobenzene, 4-cyanofluorobenzene, 2-chlorofluorobenzene, 3-chlorofluorobenzene, 4-chlorofluorobenzene, 2,4-dichlorofluorobenzene, 2,5-dichlorofluorobenzene, 2,6-dichlorofluorobenzene, 3,4-dichlorofluorobenzene, 3,5-dichlorofluorobenzene, 2,4,6-trichlorofluorobenzene, 2,4,5-trichlorofluorobenzene, pentachlorofluorobenzene, ...

13
[ 872-50-4 ]
[ 765302-52-1 ]
[ 348-59-4 ]
[ 63-74-1 ]
2-[3-(2,5-dichloro-phenoxy)-4-ethyl-phenyl]-N-(4-sulfamoyl-phenyl)-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydrogencarbonate; potassium carbonate; In water; ethyl acetate; acetone;	EXAMPLE 19 2-[3-(2,5-Dichloro-phenoxy)4-ethyl-phenyl]-N-(4-sulfamoyl-phenyl)-acetamide (I-19) step 1-To a solution of 12a (0.200 g; 0.960 mmol) and NMP (4 mL) was added K2CO3 (0.398 g; 2.88 mmol) and <strong>[348-59-4]1,4-dichloro-2-fluoro-benzene</strong> (0.124 mL; 1.056 mmol). The reaction was heated to 120 C. and monitored by TLC. After 8 h the reaction was cooled to RT and 10% HCl was added. The mixture was extracted with EtOAc and the combined extracts were washed with H2O and brine. The extracts were dried (Na2SO4) filtered and evaporated. The crude product was purified by SiO2 chromatography eluding with a gradient of hexane/EtOAc (100:0 to 60:40) to afford 142. steps 2 and 3-Hydrolysis and formation of the acid chloride were carried as described in step 7and 8 of Example 1 and used without additional purification. step 4-The acid chloride from step 3 (0.415 mmol) was dissolved in acetone (2 mL) and the flask and purged with nitrogen. NaHCO3 (0.070 g; 0.83 mmol) was added followed by 4-amino-benzenesulfonamide (0.072 g; 0.415 mmol) and water (4 mL). The mixture was sonicated for 5 min and allowed to stir for 12 h at RT. The reaction mixture was filtered and the crude product was washed sequentially with water and diethyl ether to afford I-19 Compound I-21 was prepared in the same manner except 4-amino-benzenesulfonamide was replaced with 2-chloro-phenylamine.

References: [1]Patent: US2005/239880,2005,A1 .

14
[ 348-59-4 ]
[ 2729-37-5 ]

References: [1]Journal of the American Chemical Society,1959,vol. 81,p. 94,95, 97.
[2]Patent: WO2019/67702,2019,A1 .

15
[ 351-28-0 ]
[ 348-59-4 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 1063.

16
[ 351-31-5 ]
[ 348-59-4 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 1063.

17
[ 348-59-4 ]
[ 701-00-8 ]

References: [1]Journal of general chemistry of the USSR,1962,vol. 32,p. 3078 - 3081.
Zhurnal Obshchei Khimii,1962,vol. 32,p. 3131 - 3134.

18
[ 348-59-4 ]
[ 704-08-5 ]

References: [1]Journal of general chemistry of the USSR,1962,vol. 32,p. 3078 - 3081.
Zhurnal Obshchei Khimii,1962,vol. 32,p. 3131 - 3134.

19
ethyl 4-[(4-hydroxy-1-piperidinyl)methyl]-α-phenyl-1-piperidineacetate [ No CAS ]
[ 348-59-4 ]
[ 676517-66-1 ]

Yield	Reaction Conditions	Operation in experiment
		[ETHYL 4-[(4-HYDROXY-1-PIPERIDINYL)METHYL]-?-PHENYL-1-PIPERIDINEACETATE ] (0.135 g) was dissolved in NMP (3 mL). 1, 4-Dichloro-2-fluorobenzene (0.2 mL) and potassium t- butoxide (56 mg) were added and the solution was heated to [50 C] for 40 h. The solution was cooled to ambient temperature and few drops of aqueous sodium hydroxide solution were added. The mixture was stirred for 60 h, then acetic acid (few drops) was added and the solvent was distilled. The residue was purified by HPLC (0.2% aqueous ammonia: acetonitrile; gradient 95: 5 to 50: 50) to give the title compound (21 mg). MS [[M+H] +] (ES+) 477/479 [IH] NMR [8 (CD30D)] 1.45 (1H, q), 1.68-1. 96 (9H, m), 2.16-2. 21 (2H, m), 2.25-2. 34 (2H, m), 2.57-2. 65 (3H, m), 2.80-2. 93 (2H, m), 4.29-4. 36 [(1H,] m), 4.38-4. 44 [(1H,] m), 6.83 [(1H,] dd), 7.02 (1H, d), 7.23 (1H, d), 7.32-7. 36 (3H, m), 7.44-7. 49 (2H, m)

References: [1]Patent: WO2004/29041,2004,A1 .Location in patent: Page 28-29.

20
[ 765302-52-1 ]
[ 348-59-4 ]
[ 1056987-14-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 120℃;	To a solution of 12a (0.200 g; 0.960 mmol) and NMP (4 mL) was added K2CO3 (0.398 g; 2.88 mmol) and <strong>[348-59-4]1,4-dichloro-2-fluoro-benzene</strong> (0.124 mL; 1.056 mmol). The reaction was heated to 120 C. and monitored by TLC. After 8 h the reaction was cooled to RT and 10% HCl was added. The mixture was extracted with EtOAc and the combined extracts were washed with H2O and brine. The extracts were dried (Na2SO4) filtered and evaporated. The crude product was purified by SiO2 chromatography eluting with a gradient of hexane/EtOAc (100:0 to 60:40) to afford 142.

References: [1]Patent: US2005/239881,2005,A1 .Location in patent: Page/Page column 36.

21
[ 348-59-4 ]
[ 35989-28-7 ]

Yield	Reaction Conditions	Operation in experiment
68%		Reference Example 2-46 2,5-Dichloro-4-fluorobenzoic acid Following the procedure described in Reference Example 2-25, the title compound was prepared from <strong>[348-59-4]1,4-dichloro-2-fluorobenzene</strong> (68% yield). NMR (CDCl3) delta: 7.33 (1H, d, J=8.8 Hz), 7.45 (1H, br s), 8.15 (1H, d, J=7.6 Hz).

References: [1]Patent: US2003/187014,2003,A1 .

22
[ 348-59-4 ]
[ 357406-11-2 ]

Yield	Reaction Conditions	Operation in experiment
		a 3-[(1R)-3-Azido-1-(2,5-dichlorophenoxy)propyl]isoxazole The product from Example 93(a) (0.17 g) was reacted with 2,5-dichloro-fluorobenzene (0.4 g) using the procedure described in Example 93(b) to afford the product as a gum which was carried on to the next step.

References: [1]Patent: US2003/158185,2003,A1 .

23
[ 357416-55-8 ]
[ 348-59-4 ]
[3-Cyclopropyl-3-(2.5-dichlorophenoxy)propyl]methylcarbamic Acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
175 mg (47%)	In dimethyl sulfoxide; ethyl acetate;	b [3-Cyclopropyl-3-(2.5-dichlorophenoxy)propyl]methylcarbamic Acid, 1,1-dimethylethyl Ester <strong>[348-59-4]1,4-Dichloro-2-fluorobenzene</strong> (165 mg, 1.00 mmol) and (3-cyclopropyl-3-hydroxypropyl)methylcarbamic acid, 1,1-dimethylethyl ester (230 mg, 1.00 mmol) were dissolved in dimethylsulfoxide (10 ml) under nitrogen at room temperature. To the resulting solution was added sodium hydride (60% in oil) (80 mg, 2.00 mmol). The solution was then allowed to stir at room temperature under nitrogen for 24 h. The mixture was then poured into water and extracted with diethyl ether three times. The combined organic fractions were washed with brine and dried over magnesium sulfate. The solvent was evaporated and the residue eluted down a flash chromatography column using 10% ethyl acetate/isohexane as eluent to give 175 mg (47%) of the title compound as an oil. 1H NMR 300 MHz (CDCl3) 7.26 (1H, m), 6.96 (1H, s), 6.87 (1H, m), 3.80 (1H, q), 3.42 (2H, m), 2.84 (3H, s), 2.01 (2H, m), 1.43 (9H, s), 1.10 (1H, m), 0.54 (2H, d), 0.30 (2H, bm).

References: [1]Patent: US2003/65174,2003,A1 .

24
[ 348-59-4 ]
[ 1123307-08-3 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sulfuric acid; sulfur trioxide; at 110℃;	Intermediate 124 2,5-Dichloro-4-fluorobenzenesulfonyl chlorideA mixture of 1 ,4-dichloro-2-fluorobenzene (5 g, 30.3 mmol) and fuming sulfuric acid (18- 24% SO3, 20 ml) was heated at 1 10 0C overnight. After cooling down to room temperature, the reaction mixture was carefully poured into ice (700 g). The resulting mixture was stirred at room temperature for 30 min followed by addition of ethyl acetate. The aqueous layer was isolated and concentrated under vacuum. The precipitate was filtered off to give 2,5-dichloro-4-fluorobenzenesulfonic acid as white crystals (3.33 g, 45%).The acid previously prepared (2.0 g, 8.2 mmol) and phosphorus pentachloride (5 g, 24 mmol) were heated at 110 0C overnight. After cooling down to room temperature, the reaction mixture was carefully poured into ice (50 g) The resulting mixture was stirred at room temperature for 30 min followed by addition of ethyl acetate (100 ml_). The ethyl acetate layer was isolated and concentrated under vacuum to give the title compound as yellow oil (1.29 g, 60%). 1H NMR(d6-DMSO) delta 7.62 (d, 1 H), 7.95 (d, 1 H).

References: [1]Patent: WO2009/26197,2009,A1 .Location in patent: Page/Page column 84.

25
[ 67-56-1 ]
[ 201230-82-2 ]
[ 348-59-4 ]
[ 5292-47-7 ]
4-chloro-2-fluorobenzoic acid methyl ester [ No CAS ]

References: [1]Journal of Fluorine Chemistry,2010,vol. 131,p. 81 - 85.

26
[ 623-00-7 ]
[ 348-59-4 ]
[ 1638159-35-9 ]

References: [1]Advanced Synthesis and Catalysis,2014,vol. 356,p. 1586 - 1596.
[2]Chemistry - A European Journal,2019.

27
[ 372-18-9 ]
[ 623-00-7 ]
[ 348-59-4 ]
[ 1638159-35-9 ]
2',6'-difluorobiphenyl-4-carbonytrile [ No CAS ]