3107-19-5|1,3-Dichloro-2-fluoro-5-nitrobenzene| Ambeed

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Quality Control of [ 3107-19-5 ] Purity: 98% SDS Specification

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Product Details of [ 3107-19-5 ]

CAS No. :	3107-19-5
Formula :	C₆H₂Cl₂FNO₂
M.W :	209.99
SMILES Code :	O=[N+](C1=CC(Cl)=C(F)C(Cl)=C1)[O-]
MDL No. :	MFCD00129963
InChI Key :	VMAATSFMXSMKPG-UHFFFAOYSA-N
Pubchem ID :	76554

Safety of [ 3107-19-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 3107-19-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	45.24
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	45.82 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.56
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	3.58
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.46
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.	3.3
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	1.44
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.67

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.7
Solubility	0.0418 mg/ml ; 0.000199 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.	-4.23
Solubility	0.0124 mg/ml ; 0.0000591 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately 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	-3.3
Solubility	0.106 mg/ml ; 0.000506 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	High
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	No
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.	-5.04 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	0.0
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	3.0 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<2.0
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)	1.98

Application In Synthesis of [ 3107-19-5 ]

* 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 [ 3107-19-5 ]

[ 3107-19-5 ] Synthesis Path-Downstream 1~35

1
[ 3107-19-5 ]
[ 2729-34-2 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium formate; zinc; In methanol; water; for 1.33333h;	To a solution of <strong>[3107-19-5]1,3-dichloro-2-fluoro-5-nitro-benzene</strong> (71.4 g, 340 mmol) in methanol (1.5 L) was added a solution of ammonium formate (180.2 g, 2.86 mol) in water (300 mL). Zinc dust (93.4 g, 1.43 mol) was then added in four equal portions over 20 min. The reaction was stirred for 1 h and then allowed to cool to room temperature. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated in vacuo. Ethyl acetate (300 mL) and water (300 mL) were added and the mixture was again filtered through diatomaceous earth. The layers were separated, and the aqueous layer was further extracted with ethyl acetate (350 mL). The combined organics were washed with 500 mL of brine, dried over Na2SO4, filtered, and concentrated to afford 56.4 g of the title compound as a brown solid, mJz 180.2 [M+H]+. This material was used without any further purification.
	With ammonium formate; zinc; In methanol; water; for 1.33333h;	To a solution of l,3-dichloro-2-fluoro-5-nitro-benzene (71.4 g, 340 mmol) in methanol (1.50 L) was added a solution of ammonium formate (180 g, 2.86 mol) in water (300 mL). Zinc dust (93.4 g, 1.43 mol) was then added in four equal portions over 20 min. The reaction was stirred for 1 h and then allowed to cool to room temperature. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated in vacuo. Ethyl acetate (300 mL) and water (300 mL) were added and the mixture was again filtered through diatomaceous earth. The layers were separated, and the aqueous layer was further extracted with ethyl acetate (350 mL). The combined organics were washed with 500 mL of brine, dried over Na2SO4, filtered, and concentrated to afford 56.4 g of the title compound as a brown solid, tn/z 180.2 [M+H]+. This material was used without any further purification.
	With ammonium formate;zinc; In methanol; water; at 20℃;	3,5-Dichloro-4-fluoro-phenylamine:To a solution of l,3-dichloro-2-fluoro-5-nitro-benzene (71.4 g, 340 mmol) in methanol (1.5 L) was added a solution of ammonium formate (180.2 g, 2.86 mol) in water (300 mL). Zinc dust (93.4 g, 1.43 mol) was then added in four equal portions over 20 min. The reaction was stirred for 1 h and then allowed to cool to room temperature. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated in vacuo. Ethyl acetate (300 niL) and water (300 niL) were added and the mixture was again filtered through diatomaceous earth. The layers were separated, and the aqueous layer was further extracted with ethyl acetate (350 niL). The combined organics were washed with 500 mL of brine, dried over Na2SO4, filtered, and concentrated to afford 56.4 g of the title compound as a brown solid, m/z 180.2 [M+H]+. This material was used without any further purification.

With palladium on activated charcoal; hydrogen; N-Cyanoguanidine; In ethanol; at 55℃; for 1h;

The corn stover is pulverized and freeze-dried at -10 C.After being taken out, it is mixed with melamine sodium polyphosphate and ethanol and ground to ethanol for evaporation.Preparing a mixed powder; mixing and mixing the mixed powder and dicyandiamide in a muffle furnace,The calcination treatment is carried out at 750 C for 1 h to prepare a cocatalyst; wherein, corn stalk,The mass ratio of melamine sodium polyphosphate and dicyandiamide is 3:0.023:0.5; Adding [3107-19-5]3,5-dichloro-4-fluoronitrobenzene, water and dicyandiamide to the reactor, stirring and mixing, adding palladium/carbon catalyst,a cocatalyst, introducing nitrogen gas into the reactor for 5-10 minutes to displace the air in the reactor.Then, hydrogen gas was introduced to a pressure of 18 kg, and the reaction was carried out at 55 C for 1 hour, and after the reaction was completed, it was cooled to room temperature.Detecting the content of the target product in the product; wherein [3107-19-5]3,5-dichloro-4-fluoronitrobenzene, water, dicyandiamide,The mass ratio of the palladium/carbon catalyst was 3:2:0.0015:0.001; the mass ratio of the palladium/carbon catalyst to the cocatalyst was 1:0.3.

References: [1]Journal of the American Chemical Society,1959,vol. 81,p. 94,95, 97.
[2]Patent: WO2009/70485,2009,A1 .Location in patent: Page/Page column 163.
[3]Patent: WO2010/141330,2010,A1 .Location in patent: Page/Page column 27; 28.
[4]Patent: WO2010/141273,2010,A1 .Location in patent: Page/Page column 73-74.
[5]Patent: CN108821981,2018,A .Location in patent: Paragraph 0020; 0021; 0022; 0023.

2
[ 20098-48-0 ]
[ 3107-19-5 ]

References: [1]Journal of the American Chemical Society,1959,vol. 81,p. 94,95, 97.
[2]Recueil des Travaux Chimiques des Pays-Bas,1972,vol. 91,p. 50 - 64.

3
[ 1953-54-4 ]
[ 3107-19-5 ]
5-(2,6-dichloro-4-nitro-phenoxy)-1H-indole [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1835 - 1840.

4
[ 3107-19-5 ]
[ 361436-24-0 ]
[ 439612-42-7 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1835 - 1840.

5
[ 957828-50-1 ]
[ 3107-19-5 ]
[ 957828-51-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 17h;	To a stirred solution of the 5-Methoxy-3-methyl-lH-indole-2-carboxylic acid (42 mg, 0.125 mmol), made by basic hydrolysis from the commercially available 5-Methoxy-3-methyl-l H-indole-2- carboxylic acid ethyl ester (purchased from Zerenex Molecular Ltd, UK), in DMF (3 ml) was successively added 1-hydroxybenzotriazole hydrate (60 mg, 0390mmol) and N,N-l -(3- dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloridethyl (75 mg, 0.390mmol) and isopropylamine( 40 mg, 0.39 mmol) at 0 0C. After being stirred for 1 h at 0 C the mixture was allowed to reach ambient temperature and was left stirring for 17 h.After filtration of the mixture, the filtrate was evaporated in vacuo. Purification on a silica SPE column (heptane:EtOAc 7:3) gave 5-methoxy-3-methyl-lH-indole-2-carboxylic acid <n="40"/>isopropylamide as a solid. The indole was dissolved in dichloromethane (10 mL) which was cooled to 0 0C and put under nitrogen atmosphere. Boron trifluoride dimethyl sulphide complex (3 equivalents) was added. The organic phase was washed with water, brine, dried over Na2SO4, filtrated and evaporated. The crude was utilised without further purification. The crude (30 mg) containing 5-Hydroxy-3-methyl-l H-indole-2-carboxylic acid isopropylamide, l,3-Dichloro-2- fluoro-5-nitro-benzene (22 mg, 0.1 mmol) and K2CO3 (23 mg, 0.17 mmol) was dissolved in DMSO (1.5 mL), purged with N2 and stirred at 120 0C for 17 h. The mixture was diluted with EtOAc and washed with a saturated Na2Ctheta3 solution, water, and brine. The organic phase were evaporated on silica and purified on a silica column (heptane: EtOAc, 7:3) to give 20 mg of 5-(2,6-dichloro-4- nitro-phenoxy)-3-methyl-l H-indole-2-carboxylic acid isopropylamide as a solid.The biaryl indole was dissolved in a mixture of HOAc and H2O (9: 1 , 5 mL) and Fe (27 mg) was added and the reaction was left stirring at ambient temperature for 3 h. The reaction was diluted with EtOAc and HCl (2M) was added. The organic phase was separated and the water phase extracted twice with EtOAc. The combined organic phases were washed with brine, dried with Na2SO4, filtrated and evaporated. The evaporation gave 17 mg as a brown oil which was used without further purification.To the crude (17 mg) containing 5-(4-amino-2,6-dichloro-phenoxy)-3-methyl-lH-indole-2- carboxylic acid isopropylamide, which was dissolved in CH2CI2 (10 mL) and cooled to 0 C, was added ethyl malonyl chloride (1 1 muL, 0.087 mmol) and pyridine (9 muL, 0.1 1 mmol). After 2.5 h at O0C the reaction was quenched by addition of HCl (3 mL, IM). After stirring for 10 min, additional CH2Cl2 (30 mL) and HCl (1 mL, 1 mL) was added. The organic layer was washed with HCl (IM), H2O, brine and evaporated. The crude was dissolved in THF (5 ml) and LiOH (IM, 2 ml) and left overnight. The reaction mixture was acidified to pH 3 with HCl (2M). EtOAc was added and the organic phase was washed with brine, dried with Na2SO4, filtrated and evaporated. The ethyl ester was dissolved in THF (5 ml) and LiOH (IM, 2 ml) was added. The reaction was left stirring for 4 days at ambient temperature. HCI (2M) was added until pH 3 was reached. Extraction with EtOAc (2x20 ml), washed with brine, dried with Na2SO4 and evaporated. The crude was purified by semi-preparative HPLC (Zorbax CombiHT (SB-C8 50x21.2 mm, 5mu) Mobile Phase: Solvent A. Water with 0.5% formic acid; Solvent B: acetonitrile. Gradient: 2 min 80% of A then over 8 min to 5% of A) giving 2.5 mg as a solid (yield: 4.1 %) LCMS.

References: [1]Patent: WO2007/134864,2007,A1 .Location in patent: Page/Page column 39.

6
[ 2731-06-8 ]
[ 3107-19-5 ]
[ 1132682-58-6 ]

Yield	Reaction Conditions	Operation in experiment
28%	With sodium hydrogencarbonate; In dimethyl sulfoxide; at 60℃;	A mixture of 1 ,3-dichloro-2-fluoro-5-nitrobenzene (0.0048 mol), 1 H-indole-2-methyl-3- ethanamine (0.004 mol) and NaHCO3 (0.0048 mol) in DMSO (10ml) was stirred at 600C overnight, cooled to room temperature. Ice water was added. The precipitate was filtered, washed with CH3CN and dried, yielding 0.48g (28%) of intermediate 5b (M. P.: 147C).

References: [1]Patent: WO2009/37308,2009,A1 .Location in patent: Page/Page column 72.

7
[ 3107-19-5 ]
[ 3610-36-4 ]
[ 1132682-60-0 ]

Yield	Reaction Conditions	Operation in experiment
66%	With sodium hydrogencarbonate; In dimethyl sulfoxide; at 60℃;	A mixture of 1 ,3-dichloro-2-fluoro-5-nitrobenzene (0.0048 mol), 1 /-/-indole-6-methoxy-3- ethanamine (0.0048 mol) and NaHCO3 (0.0057 mol) in DMSO (10ml) was stirred at 600C overnight, cooled to room temperature. Ice water was added. The precipitate was filtered, washed with CH3CN and the solvent was evaporated till dryness, yielding 1.2g (66%) of intermediate 5c (M. P.: 1 16C)

References: [1]Patent: WO2009/37308,2009,A1 .Location in patent: Page/Page column 72.

8
[ 61-54-1 ]
[ 3107-19-5 ]
[ 1132682-56-4 ]

Yield	Reaction Conditions	Operation in experiment
62%	With sodium hydrogencarbonate; In dimethyl sulfoxide; at 60℃;	A mixture of 1 ,3-dichloro-2-fluoro-5-nitrobenzene (0.0048 mol), 1 /-/-indole-3-ethanamine (0.0048 mol) and NaHCO3 (0.0057 mol) in DMSO (10ml) was stirred at 600C overnight, cooled to room temperature. Ice water was added. The mixture was extracted with EtOAc. The organic layer was decanted, dried (MgSO4), filtered off and the solvent was evaporated till dryness. The residue was crystallized from CH3CN/DIPE. The precipitate was filtered off and dried, yielding 1.03g (62%) of intermediate 5a (M. P.: 98C).

References: [1]Patent: WO2009/37308,2009,A1 .Location in patent: Page/Page column 71.

9
[ 3107-19-5 ]
[ 1276039-75-8 ]
[ 1276040-04-0 ]

Yield	Reaction Conditions	Operation in experiment
		Phenol 24a2 (100 mg, 0.33 mmol) is coupled to <strong>[3107-19-5]3,5-dichloro-4-fluoronitrobenzene</strong> (84 mg, 0.40 mmol) using the protocol described in example 5C step 1. The mixture is diluted with EtOAc then washed with water and brine. The organic phase is dried with MgS04, filtered and concentrated. The residue is taken up in THF (8 mL). To the mixture is added 1 N HCI (5 mL) and tin (110 mg, 0.90 mmol). The mixture is stirred 2 h at RT before being filtered through celite and concentrated. Crude 24b1 is utilized in the next step without further purification.

References: [1]Patent: WO2011/32277,2011,A1 .Location in patent: Page/Page column 56-57.

10
[ 3107-19-5 ]
[ 1276039-75-8 ]
[ 1276034-49-1 ]

Yield	Reaction Conditions	Operation in experiment
		Phenol 24a2 (100 mg, 0.33 mmol) is coupled to <strong>[3107-19-5]3,5-dichloro-4-fluoronitrobenzene</strong> (84 mg, 0.40 mmol) using the protocol described in example 5C step 1. The mixture is diluted with EtOAc then washed with water and brine. The organic phase is dried with MgS04, filtered and concentrated. The residue is taken up in THF (8 mL). To the mixture is added 1 N HCI (5 mL) and tin (110 mg, 0.90 mmol). The mixture is stirred 2 h at RT then heated to 60 C and stirring is continued for 24 h. The mixture is concentrated and the residue is diluted with EtOAc then washed with sat. aq. NaHC03 and brine. The organic phase is dried with MgS04, filtered and concentrated. The residue is taken up in DMSO then injected onto a prep. HPLC to isolate 2004.

References: [1]Patent: WO2011/32277,2011,A1 .Location in patent: Page/Page column 58.

11
[ 3107-19-5 ]
[ 42433-74-9 ]
1,3-dichloro-2-(hexyl-2-methoxyphenoxy)-5-nitrobenzene [ No CAS ]

References: [1]ChemMedChem,2014,vol. 9,p. 776 - 791.

12
[ 3107-19-5 ]
1-(2,6-dichlorophenoxy)-3-hexyl-2-methoxybenzene [ No CAS ]

References: [1]ChemMedChem,2014,vol. 9,p. 776 - 791.

13
[ 3107-19-5 ]
C₁₉H₂₃Cl₂NO₂ [ No CAS ]

References: [1]ChemMedChem,2014,vol. 9,p. 776 - 791.

14
[ 142-08-5 ]
[ 3107-19-5 ]
[ 1620783-12-1 ]

Yield	Reaction Conditions	Operation in experiment
40%	With potassium tert-butylate; In N,N-dimethyl-formamide; at 0 - 20℃;Inert atmosphere;	Example 3, Procedure A N3-[3,5-Dichloro-4-(pyridin-2-yloxy)-phenyl]-lH-[l,2,4]triazole-3,5-diamine (Compound 26) 2-(2,6-Dichloro-4-nitro-phenoxy)-pyridine O In a 50 mL round-bottomed flask, potassium tert-butoxide (3.53 g, 31.5 mmol, Eq: 1.50) and pyridin-2(lH)-one (2 g, 21.0 mmol, Eq: 1.00) were combined with DMF (25.0 ml) to give a light brown suspension at 0C under nitrogen. l,3-Dichloro-2-fluoro-5-nitrobenzene (4.42 g, 21.0 mmol, Eq: 1.00) was added. The reaction was stirred overnight at room temperature. The reaction mixture was diluted with CH2CI2 (50 mL), washed with H2O (25 mL) and brine (25 mL). The organic layer was dried over anhydrous MgS04, filtered and volatiles were removed under reduced pressure to yield an oil from which the compound was isolated by column chromatography (Hexanes/EtOAc = 70/30) to give an off-white solid 2.4 g (40%). MH+ 284.9

References: [1]Patent: WO2014/114573,2014,A1 .Location in patent: Page/Page column 87-88.

15
[ 3107-19-5 ]
[ 108-98-5 ]
[ 180253-72-9 ]

Yield	Reaction Conditions	Operation in experiment
96.7%	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 8h;	N3-(3,5-Dichloro-4-phenylsulfanyl-phenyl)-lH-[l,2,4]triazole-3,5-diamine (Compound 4) (2,6-dichloro-4-nitrophenyl)(phenyl)sulfane O In a 500-mL round-bottomed flask, l,3-dichloro-2-fluoro-5-nitrobenzene (4.0 g, 19.0 mmol, Eq: 1.00), potassium carbonate (6.6 g, 47.8 mmol, Eq: 2.51) and benzenethiol (2.9 g, 2.7 ml, 26.3 mmol, Eq: 1.38) were combined with N,N-dimethylformamide (40 ml) to give a white suspension. This mixture was stirred at 100 C for 8 hours. After this time, reverse-phase HPLC indicated complete conversion of the starting material to a single new product. The reaction mixture was combined with ice water, giving a yellow suspension. This suspension was extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered, and concentrated to afford a brown oil. 1H NMR of the crude product was consistent with a new product, but excess Nu,Nu-dimethylformamide and thiophenol also appeared to be present. The crude product was loaded directly onto a 210 g Analogix column. Flash chromatography (using 100% hexanes) provided the purified product. Obtained 5.53 g (96.7%) of (2,6-dichloro-4- nitrophenyl)(phenyl)sulfane as an oily yellow solid.

References: [1]Patent: WO2014/114573,2014,A1 .Location in patent: Page/Page column 41-42.

16
[ 3107-19-5 ]
[ 1620782-69-5 ]