[ CAS No. 347-84-2 ] {[proInfo.proName]}

Name: 347-84-2|1-(4-Fluorophenyl)-2-phenylethanone|98%
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Quality Control of [ 347-84-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 347-84-2 ]

SDS Specification

Alternatived Products of [ 347-84-2 ]

Product Details of [ 347-84-2 ]

CAS No. :	347-84-2	MDL No. :	MFCD00017960
Formula :	C₁₄H₁₁FO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YFYKGCQUWKAFLW-UHFFFAOYSA-N
M.W :	214.24	Pubchem ID :	318235
Synonyms :

Calculated chemistry of [ 347-84-2 ] Expand+

Physicochemical Properties

Num. heavy atoms :	16
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.07
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	61.08
TPSA :	17.07 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.28 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.28
Log Po/w (XLOGP3) :	3.28
Log Po/w (WLOGP) :	3.67
Log Po/w (MLOGP) :	3.66
Log Po/w (SILICOS-IT) :	4.17
Consensus Log Po/w :	3.41

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.59
Solubility :	0.0549 mg/ml ; 0.000256 mol/l
Class :	Soluble
Log S (Ali) :	-3.31
Solubility :	0.104 mg/ml ; 0.000486 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-5.55
Solubility :	0.000598 mg/ml ; 0.00000279 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.57

Safety of [ 347-84-2 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 347-84-2 ]

* 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 [ 347-84-2 ]
Downstream synthetic route of [ 347-84-2 ]

[ 347-84-2 ] Synthesis Path-Upstream 1~1

1
[ 347-84-2 ]
[ 88675-31-4 ]

Yield	Reaction Conditions	Operation in experiment
94.8%	With hydrogen bromide; bromine; acetic acid In dichloromethane at 26℃;	EXAMPLE-2; 2-Bromo- 1 -(4-fluorophenyl)-2-phenylethanone; Methylene chloride (1L) is taken in a 4 necked RB flask equipped with mechanical strring rod, pressure equalization funnel and a CaCl₂ guard tube. 100 g (0.466 mol) of l-(4-Fluorophenyl)-2-phenyl ethanone is introduced in to the above flask and stirred for 5 minutes to obtain a clear solution.2ml of a 30percent hydrobromic acid in acetic acid is then added , followed by gradual addition of a cold solution of bromine (73 g, 0.456 mole) in 200ml of methylene chloride at 26+/-2°C. Bromine solution is added in such a manner that it is consumed instantly as indicated by colouration of reaction mixture. After addition of bromine solution the reaction mixture is cooled to 19+/-1°C , treated with 5percent aqueous sodium sulphite ( 200 ml) and stirred for about lhr at 21.5+/-3.5°C. The organic layer is then separated and is subjected to the above operation twice with 5percent aqueous sodium sulphite (2 x 200ml).The organic layer is then stirred with 5percent aqueous sodium bicarbonate (200 ml) for about 1 hr at 21.5+/-3.5 C and separated.. The organic layer is finally stirred with 5percent aqueous sodium chloride(200ml) and separated. The organic layer is dried over sodium sulphate and filtered. Methylene chloride is removed by distillation and the syrup thus obtained solidified on standing in to a pale orange coloured solid. Yield 129 g ( 94.8percent)
92%	With copper(II) nitrate trihydrate; hydrogen bromide; oxygen In acetic acid at 60℃; for 4.5 h; Green chemistry	The representative example of oxidative bromination is described as follows: A mixture of 1.2 g acetophenone 1a (10 mmol) and 0.121 g Cu(NO₃)₂•3H₂O (0.5mmol) was stirred and an oxygen balloon (about 0.5–1 L) was attached to the reaction system. Then 8mol/L aqueous solution of hydrobromic acid (1.5mL, 12mmol) was added dropwise to the mixture. The reaction mixture was then stirred at 70°C and monitored by TLC or GC. After the completion of the reaction, the mixture was extracted with CH₂Cl₂. The organic extract was first washed with 5percent sodium sulfite, saturated sodium bicarbonate solution, and then water and finally dried over anhydrous magnesium sulfate. The solvent was removed under vacuum and the residue was purified by column chromatography (silica gel, petroleum ether/dichloromethane 3:1) to afford the product, α-bromoacetophenone (2a) in 1.81 g, yield: 91percent.
90%	at 40℃; for 16 h;	The third step, 10.7g 4-fluorophenylacetophenone was dissolved in 100ml of glacial acetic acid, 40percent hydrobromic acid was added 15ml, stirred,Slowly dropping 30percent mass fraction of hydrogen peroxide 9ml, 40 reaction 16h, TLC trace showed the end of the reaction.Unreacted bromine was removed by adding saturated aqueous sodium sulfite to the reaction mixture.The reaction mixture was extracted with 200 ml of ethyl acetate and an appropriate amount of aqueous sodium carbonate. The organic layer was separated and the organic layer was washed twice with aqueous sodium carbonate solution and dried over anhydrous magnesium sulfate.After filtration and spin drying, 13.25 g of 2-bromo-1- (4-fluorophenyl) -acetophenone was obtained as a yellow thick liquid in a yield of 90percent.

88%	With copper(ll) bromide In dichloromethane; ethyl acetate for 18 h; Reflux; Inert atmosphere	General procedure: Copper(II) bromide (CuBr₂, 268 mg, 1.2 mmol) was added to a solution of skeleton 5 (1.0 mmol) in the co-solvent of EtOAc and CH₂Cl₂ (1:1, 20 mL), at 25 °C. The reaction mixture was stirred at reflux for 18 h. The reaction mixture was cooled to 25 °C. Saturated NaHCO₃(5 mL) was added to the reaction mixture and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product. Purification on silica gel (hexanes/EtOAc = 10/1-6/1) afforded skeletons 3 and 6.
85%	Stage #1: With hydrogen bromide In water at 20℃; for 0.0833333 h; Darkness Stage #2: With bromine In water at 20℃; for 5 h; Stage #3: With dihydrogen peroxide In water at 20℃; for 12 h;	Compound 4 (5.00 g, 23.34 mmol) was suspended in water (15 mL) in a flaskcovered with aluminum foil. Five drops of 40 percent aqueous solution of HBr was added.The mixture was stirred at room temperature for 5 min, Br2 (2.05 g, 12.84 mmol) wasadded dropwise. The reaction mixture was stirred at room temperature for 5 h, and30 percent aqueous solution of H2O2 (6.5 mL, 25.70 mmol) was slowly added. After 12 h,dichloromethane (30 mL) was added and the organic layer was washed with 5 percentaqueous sodium sulfite (10 mL) and 5 percent aqueous sodium chloride (2×20 mL) andthen dried over anhydrous magnesium sulfate. The organic mixture was concentrated to give a light yellow oil 5 (5.82 g, 85 percent yield). 1H NMR (600 MHz, CDCl3) δ: 8.01–7.98 (m,2H), 7.49 (d, J=7.2 Hz,2H), 7.36–7.30 (m,3H), 7.07 (t, J=8.6 Hz,2H), 6.32 (s,1H). 13C NMR (150 MHz, CDCl3) δ: 189.33, 166.29, 164.59,135.52, 131.69, 131.63, 130.04, 128.89, 128.74, 115.71, 115.57, 51.07.

Reference： [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 15, p. 6479 - 6494
[2] Patent: WO2012/143933, 2012, A1, . Location in patent: Page/Page column 13-14
[3] Synthetic Communications, 2016, vol. 46, # 2, p. 165 - 168
[4] Patent: CN106397296, 2017, A, . Location in patent: Paragraph 0018; 0021; 0024; 0027; 0030; 0033; 0036; 0039
[5] Tetrahedron, 2017, vol. 73, # 34, p. 5207 - 5213
[6] Synthetic Communications, 2015, vol. 45, # 24, p. 2832 - 2840
[7] Tetrahedron, 1969, vol. 25, p. 969 - 984

[ 347-84-2 ] Synthesis Path-Downstream 1~110

1
[ 347-84-2 ]
[ 323-28-4 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1949,vol. 68,p. 781,785

2
[ 347-84-2 ]
[ 91-56-5 ]
[ 436-02-2 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1949,vol. 68,p. 781,785

3
[ 347-84-2 ]
[ 87-48-9 ]
[ 361-28-4 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1949,vol. 68,p. 781,785

4
[ 347-84-2 ]
[ 100-63-0 ]
[ 436-53-3 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1949,vol. 68,p. 781,785

5
[ 462-06-6 ]
[ 103-80-0 ]
[ 347-84-2 ]

Yield	Reaction Conditions	Operation in experiment
80%	With zeolite; In dichloromethane; at 10℃; for 2h;Cooling with ice; Molecular sieve;	The second step, the 10.6g of fluorobenzene was added to 100ml of dichloromethane was stirred under ice bath was added 13g zeolite molecular sieves,Then ice-bath conditions to the above solution was added dropwise 15.4g of phenylacetyl chloride in dichloromethane 40ml, the reaction was kept dropwise during the addition of the temperature does not exceed 10 , the reaction was continued dropwise addition 2h,The TLC trace shows the reaction is over. Filtration and spin-drying gave a light yellow solid which was recrystallized to give 17.12 g of 4-fluorophenylacetophenone in a yield of 80%.
77.7%	With aluminum (III) chloride; at -10 - 0℃;Inert atmosphere;Product distribution / selectivity;	EXAMPLE- 1; l-(4-Fluorophenyl)-2-phenyl ethanone (II); Fluorobenzene (100 g, 1.04 mol ) is taken in a clean and dry 4 necked RJB flask equipped with mechanical stirring rod, pressure equalization funnel, N2 inlet and a CaCl2 guard tube. The contents of the flask are cooled to 0C in an ice bath under a stream of N2 gas. 103 g (0.768 mol) of powdered aluminum chloride are added into the flask under stirring. The contents of the flask are further cooled to -10C by adding common salt to ice bath. Phenyl acetyl chloride (1 10.75 g , 0.717 moles) is placed in the pressure equalization funnel fitted to the flask and added drop wise manner in 2- 2 ½ hours ,while maintaining the temperature of the reaction between -10 to 0C. After the addition the reaction is maintained for a further period of 2 hours between -10 to 0C. In process sample of reaction mixture showed the area % of 1 -(4-Fluorophenyl)- 2-phenyl ethanone by HPLC as 98.55%. The reaction mixture is then poured slowly into a mixture of ice (300 g), water (300ml) and Conc.hydrochloric acid (30 ml) while maintain the temperature between -10 to 5C the contents are stirred for ½ hr at this temperature. The solid thus obtained is washed successively with water (2 x 200ml) and is transferred into RB flask. The wet solid is dissolved in 250 ml of Petroleum Ether (60-80C) at 62.5+/-2.5C. The contents are cooled to 30C, and water thus separated from organic phase is removed. The organic phase is cooled to 18+/-2C under stirring and maintained for additional 1 hr at 18+/-2C. The product is isolated on a filter and washed with cold Petrolueum Ether(25 ml) and dried at 42.5+/-2.5C till water content is <0.5%. Yield 122 g (77.7%)
70%	With aluminum (III) chloride; at 0 - 5℃; for 1h;	After cooling fluorobenzene (216 g, 8 eq) and AlCl 3 (75 g, 1.2 eq) to 0-5 C., 2-phenylacetyl chloride (62 ml, 1 eq) was slowly added dropwise,Stirred at the same temperature for 1 hour.2 N HCl (0.28 L) was added to the reaction solution.NaHCO 3 saturated aqueous solution (0.11 L),Washed with distilled water (0.11 L) and brine (0.11 L).The organic layer was concentrated under reduced pressure and IPA (0.26 L) was added thereto.The reaction was carried out at 55 to 60 C. for 1 hour, at 20 to 30 C. for 1 hour,Stirring at 0-5 C. for 2 hours yielded a solid.The resulting solid was filtered off and washed with IPA (0.06 L),Vacuum drying at 50-55 C. for 12 hours gave the title compound.Solid 80 g (yield 70%);

69%

With aluminum (III) chloride; at 40 - 80℃; for 5h;Cooling with ice;

15 g of aluminum trichloride and 62 g of fluorobenzene were added to the reaction flask, and 21 g of phenylacetyl chloride was added dropwise under ice-Temperature control at 40 C;Heating to 80 C; heating for 5 hours, TLC analysis of raw materials completely complete, down to room temperature, dark green solution; into 55g crushed ice and 35ml2mol / L hydrochloric acid mixture, the control temperature below 60 , The organic layer by adding 120mL saturated sodium bicarbonate to adjust the pH, layer; water layer with the appropriate amount of fluorobenzene reverse extraction, combined organic layer, concentrated to dry, adding appropriate amount of petroleum ether recrystallization, 20g 4 - fluorophenyl acetophenone,Yield 69%;

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 4277 - 4281
Angew. Chem.,2017,vol. 129,p. 4341 - 4345,5
[2]Tetrahedron Letters,2015,vol. 56,p. 1575 - 1580
[3]Patent: CN106397296,2017,A .Location in patent: Paragraph 0018; 0020; 0024; 0026; 0030; 0032; 0036; 0038
[4]Patent: WO2012/143933,2012,A1 .Location in patent: Page/Page column 12-13
[5]Patent: KR102001835,2019,B1 .Location in patent: Paragraph 0398-0402
[6]Patent: CN103420823,2016,B .Location in patent: Paragraph 0038
[7]RSC Advances,2014,vol. 4,p. 38726 - 38742
[8]Phosphorus, Sulfur and Silicon and the Related Elements,2005,vol. 180,p. 1593 - 1600
[9]Chemische Berichte,1980,vol. 113,p. 183 - 192
[10]Recueil des Travaux Chimiques des Pays-Bas,1949,vol. 68,p. 781,785
[11]Tetrahedron,1970,vol. 26,p. 5557 - 5579
[12]Journal of the American Chemical Society,1991,vol. 113,p. 9640 - 9654
[13]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1881 - 1893
[14]Chemistry of Heterocyclic Compounds,2006,vol. 42,p. 901 - 906
[15]European Journal of Medicinal Chemistry,2008,vol. 43,p. 2004 - 2010

6
[ 347-84-2 ]
[ 143-33-9 ]
[ 60694-99-7 ]

Reference： [1]Journal of the American Chemical Society,1991,vol. 113,p. 9640 - 9654

7
[ 347-84-2 ]
[ 88522-72-9 ]

Yield	Reaction Conditions	Operation in experiment
71%		0.5 g of l-(4-fluorphenyl)-2-phenylethanone (2.3 mmol) was dissolved in 50 ml of tetrahydrofurane, and then cooled to a temperature below O0C. 1.8 ml of lithium diiso- propylamide (3.5 mmol) was dissolved in 5 ml of tetrahydrofurane, and then added dropwise to the l-(4-fluorphenyl)-2-phenylethanone solution cooled to a temperature below O0C. 30 minutes after the dropwise addition, 1 g of camphorsulfonyloxaziridine (4.7 mmol) was dissolve in 5 ml of tetrahydrofurane, added to the l-(4-fluorphenyl)-2-phenylethanone solution cooled to a temperature below O0C, and then kept at a room temperature. After 30 minutes, the reaction of the resulting mixture was stopped with a saturated ammonium chloride solution, and then extracted by adding ethylacetate to the mixture. The extracted ethylacetate was washed with water and saturated saline, and then concentrated under a reduced pressure. Then, the resulting concentrate was purified with column chromatography to obtain 0.38 g of white crystals (Yield: 71%).[87] IH-NMR (CDC13)delta: 5.9 (d, IH), 7.05 (m, 2H), 7.28-7.40 (m, 5H), 7.92-8.20 (m,2H)[88] Mass (M+l): 231

Reference： [1]Patent: WO2009/84827,2009,A2 .Location in patent: Page/Page column 5; 8
[2]Journal of Medicinal Chemistry,1993,vol. 36,p. 3658 - 3662

8
[ 347-84-2 ]
[ 1576-35-8 ]
[ 73424-43-8 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 183 - 192
[2]Organic Letters,2015,vol. 17,p. 1692 - 1695

9
[ 395-21-1 ]
[ 347-84-2 ]
[ 347-91-1 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1989,vol. 62,p. 3182 - 3186

10
[ 347-84-2 ]
[ 23075-70-9 ]

Reference： [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 3913 - 3916
Angew. Chem.,2014,vol. 126,p. 3994 - 3997,4
[2]Angewandte Chemie - International Edition,2017,vol. 56,p. 4277 - 4281
Angew. Chem.,2017,vol. 129,p. 4341 - 4345,5
[3]Tetrahedron,1970,vol. 26,p. 5557 - 5579

11
[ 347-84-2 ]
[ 31464-85-4 ]

Reference： [1]Tetrahedron,1970,vol. 26,p. 5557 - 5579

12
[ 347-84-2 ]
[ 88675-31-4 ]

Yield	Reaction Conditions	Operation in experiment
94.8%	With hydrogen bromide; bromine; acetic acid; In dichloromethane; at 26℃;Product distribution / selectivity;	EXAMPLE-2; 2-Bromo- 1 -(4-fluorophenyl)-2-phenylethanone; Methylene chloride (1L) is taken in a 4 necked RB flask equipped with mechanical strring rod, pressure equalization funnel and a CaCl2 guard tube. 100 g (0.466 mol) of l-(4-Fluorophenyl)-2-phenyl ethanone is introduced in to the above flask and stirred for 5 minutes to obtain a clear solution.2ml of a 30% hydrobromic acid in acetic acid is then added , followed by gradual addition of a cold solution of bromine (73 g, 0.456 mole) in 200ml of methylene chloride at 26+/-2C. Bromine solution is added in such a manner that it is consumed instantly as indicated by colouration of reaction mixture. After addition of bromine solution the reaction mixture is cooled to 19+/-1C , treated with 5%» aqueous sodium sulphite ( 200 ml) and stirred for about lhr at 21.5+/-3.5C. The organic layer is then separated and is subjected to the above operation twice with 5% aqueous sodium sulphite (2 x 200ml).The organic layer is then stirred with 5% aqueous sodium bicarbonate (200 ml) for about 1 hr at 21.5+/-3.5 C and separated.. The organic layer is finally stirred with 5% aqueous sodium chloride(200ml) and separated. The organic layer is dried over sodium sulphate and filtered. Methylene chloride is removed by distillation and the syrup thus obtained solidified on standing in to a pale orange coloured solid. Yield 129 g ( 94.8%)
93%	With hydrogen bromide; bromine; In dichloromethane; at 0 - 5℃;	HBr (2.88 ml, 0.01 eq) was added dropwise to the reaction solution of 1- (4-fluorophenyl) -2-phenylethan-1-one (144 g, 1 eq) obtained in step 1 in CH 2 Cl 2 (1.4 L). After cooling to 0-5 .Br 2 (34.56 ml, 2 eq) was diluted with CH 2 Cl 2 (0.29 L) and added dropwise to 1- (4-fluorophenyl) -2-phenylethan-1-one solution.next,5% Na 2 SO 3 (0.29 L) was added to the reaction solution, and the mixture was stirred at 20 to 25 C. for 1 hour.The CH2Cl2 layer was separated and washed twice more with 5% Na2SO3 (0.29 L). 5% NaHCO 3 (0.29 L) was added and stirred at 20-25 C. for 1 hour. The CH 2 Cl 2 layer was separated and washed with 5% NaCl (0.29 L). MgSO 4 (30 g) was added to the organic layer, and dried and filtered.The filtrate was concentrated under reduced pressure, hexane (0.4 L) was added thereto, and stirred at 20 to 30 C. for 1 hour and 0 to 5 C. for 2 hours to form a solid. The resulting solid was filtered, washed with hexane (0.2 L) and vacuum dried at 25-30 C. for 12 hours to afford the title compound.184 g of solids (yield 93%);
92%	With copper(II) nitrate trihydrate; hydrogen bromide; oxygen; In acetic acid; at 60℃; for 4.5h;Green chemistry;	The representative example of oxidative bromination is described as follows: A mixture of 1.2 g acetophenone 1a (10 mmol) and 0.121 g Cu(NO3)2?3H2O (0.5mmol) was stirred and an oxygen balloon (about 0.5-1 L) was attached to the reaction system. Then 8mol/L aqueous solution of hydrobromic acid (1.5mL, 12mmol) was added dropwise to the mixture. The reaction mixture was then stirred at 70C and monitored by TLC or GC. After the completion of the reaction, the mixture was extracted with CH2Cl2. The organic extract was first washed with 5% sodium sulfite, saturated sodium bicarbonate solution, and then water and finally dried over anhydrous magnesium sulfate. The solvent was removed under vacuum and the residue was purified by column chromatography (silica gel, petroleum ether/dichloromethane 3:1) to afford the product, alpha-bromoacetophenone (2a) in 1.81 g, yield: 91%.

92%	With dihydrogen peroxide; acetic acid; potassium bromide; In dichloromethane; water; at 0 - 5℃; for 2h;	The bromination reaction using the bromide prepared above, specifically, 8.7 g of 4'-fluorophenyl-2-phenylethanone,80 mL of dichloromethane and 10 mL of water were added to a 250 mL three-necked flask, and then 8.6 g of the above-mentioned dried potassium bromide-containing solid was added.Stir and lower the temperature to 0-5 C, then add 3 mL of acetic acid dropwise. After the addition is completed, continue to maintain the temperature of 0-5 C and add 30% hydrogen peroxide 2.44 g.After the completion of the dropwise addition, the reaction was kept for 2 hours, and then liquid separation was carried out.18 mL of a 5% aqueous solution of sodium sulfite was added dropwise to the organic phase, and the mixture was stirred for 1 hour, and then separated.The organic phase was washed once with 18 mL of 5% aqueous sodium sulfite solution and then with 18 mL of 5% carbon.The aqueous sodium hydrogencarbonate solution and the 18 mL saturated saline solution were each washed once.The organic phase was dried over sodium sulfate, concentrated by filtration and solidified to give 10.9 g of pale yellow solid.2-bromo-1-(4'-fluorophenyl)-2-phenylethanone (Compound I), yield 92%, HPLC purity97.4%.
90%	With hydrogen bromide; dihydrogen peroxide; acetic acid; at 40℃; for 16h;	The third step, 10.7g 4-fluorophenylacetophenone was dissolved in 100ml of glacial acetic acid, 40% hydrobromic acid was added 15ml, stirred,Slowly dropping 30% mass fraction of hydrogen peroxide 9ml, 40 reaction 16h, TLC trace showed the end of the reaction.Unreacted bromine was removed by adding saturated aqueous sodium sulfite to the reaction mixture.The reaction mixture was extracted with 200 ml of ethyl acetate and an appropriate amount of aqueous sodium carbonate. The organic layer was separated and the organic layer was washed twice with aqueous sodium carbonate solution and dried over anhydrous magnesium sulfate.After filtration and spin drying, 13.25 g of 2-bromo-1- (4-fluorophenyl) -acetophenone was obtained as a yellow thick liquid in a yield of 90%.
88%	With copper(ll) bromide; In dichloromethane; ethyl acetate; for 18h;Reflux; Inert atmosphere;	General procedure: Copper(II) bromide (CuBr2, 268 mg, 1.2 mmol) was added to a solution of skeleton 5 (1.0 mmol) in the co-solvent of EtOAc and CH2Cl2 (1:1, 20 mL), at 25 C. The reaction mixture was stirred at reflux for 18 h. The reaction mixture was cooled to 25 C. Saturated NaHCO3 (5 mL) was added to the reaction mixture and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product. Purification on silica gel (hexanes/EtOAc = 10/1-6/1) afforded skeletons 3 and 6.
85%		Compound 4 (5.00 g, 23.34 mmol) was suspended in water (15 mL) in a flaskcovered with aluminum foil. Five drops of 40 % aqueous solution of HBr was added.The mixture was stirred at room temperature for 5 min, Br2 (2.05 g, 12.84 mmol) wasadded dropwise. The reaction mixture was stirred at room temperature for 5 h, and30 % aqueous solution of H2O2 (6.5 mL, 25.70 mmol) was slowly added. After 12 h,dichloromethane (30 mL) was added and the organic layer was washed with 5 %aqueous sodium sulfite (10 mL) and 5 % aqueous sodium chloride (2×20 mL) andthen dried over anhydrous magnesium sulfate. The organic mixture was concentrated to give a light yellow oil 5 (5.82 g, 85 % yield). 1H NMR (600 MHz, CDCl3) delta: 8.01-7.98 (m,2H), 7.49 (d, J=7.2 Hz,2H), 7.36-7.30 (m,3H), 7.07 (t, J=8.6 Hz,2H), 6.32 (s,1H). 13C NMR (150 MHz, CDCl3) delta: 189.33, 166.29, 164.59,135.52, 131.69, 131.63, 130.04, 128.89, 128.74, 115.71, 115.57, 51.07.

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6479 - 6494
[2]Patent: WO2012/143933,2012,A1 .Location in patent: Page/Page column 13-14
[3]Patent: KR102001835,2019,B1 .Location in patent: Paragraph 0378; 0403-0406
[4]Synthetic Communications,2016,vol. 46,p. 165 - 168
[5]Patent: CN109836350,2019,A .Location in patent: Paragraph 0049-0050; 0053; 0055-0057; 0059-0060
[6]Patent: CN106397296,2017,A .Location in patent: Paragraph 0018; 0021; 0024; 0027; 0030; 0033; 0036; 0039
[7]Tetrahedron,2017,vol. 73,p. 5207 - 5213
[8]Synthetic Communications,2015,vol. 45,p. 2832 - 2840
[9]Tetrahedron,1969,vol. 25,p. 969 - 984

13
[ 405-29-8 ]
[ 1600-27-7 ]
[ 347-84-2 ]
Acetic acid (Z)-2-(4-fluoro-phenyl)-1-phenyl-vinyl ester [ No CAS ]
Acetic acid (Z)-1-(4-fluoro-phenyl)-2-phenyl-vinyl ester [ No CAS ]

Reference： [1]Journal of Chemical Research, Miniprint,1996,p. 689 - 697

15
[ 100-39-0 ]
[ 403-43-0 ]
[ 347-84-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 65 - 68
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 1511 - 1517

16
[ 347-84-2 ]
[ 546-67-8 ]
acetic acid 2-(4-fluoro-phenyl)-2-oxo-1-phenyl-ethyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 65 - 68

17
[ 50-00-0 ]
[ 347-84-2 ]
1-(4-fluorophenyl)-2-phenylprop-2-en-1-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 627 - 643
[2]Organic and Biomolecular Chemistry,2010,vol. 8,p. 3287 - 3293

18
[ 347-84-2 ]
[ 185345-82-8 ]

Reference： [1]RSC Advances,2014,vol. 4,p. 38726 - 38742
[2]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1881 - 1893

19
[ 347-84-2 ]
[ 563-41-7 ]
[ 323-28-4 ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2005,vol. 180,p. 1593 - 1600

20
(E/Z)-1-methoxy-2-phenyl-1-(4-fluorophenyl)ethene [ No CAS ]
[ 347-84-2 ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 459 - 462

21
[ 1765-93-1 ]
[ 140-29-4 ]
[ 347-84-2 ]

Yield	Reaction Conditions	Operation in experiment
88%	With bathophenanthroline; water; copper diacetate; manganese(III) triacetate dihydrate; In 1,4-dioxane; at 90℃;	General procedure: In a 25mL round bottom flask (oven-dried overnight) was added the phenyl boronic acid (1a, 1.0 mmol) followed by the addition of 1,4-dioxane (6mL). To this solution, manganese (III) acetate. dihydrate (5mol%), Bphen (3e, 10mol%), Cu(OAc)2 (5mol%), nitrile (0.5mmol) and water (0.5mmol) were added sequentially. The reaction was then stirred at room temperature for 10min and slowly brought to 90C under air. The reaction was allowed to run for overnight at the same temperature. After the completion, the reaction mixture was quenched and extracted with ethyl acetate and water. The organic layer was collected, and the aqueous layer was again extracted with ethyl acetate for three more times. The combined organic layer was further washed with sodium bicarbonate and brine solution. The organic layer was then dried over sodium sulfate, filtered and evaporated using rotavap. The crude compound obtained was further purified using column chromatography (EA:hexane 10:90).

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 3816 - 3820
[2]Organic Letters,2006,vol. 8,p. 5987 - 5990
[3]Tetrahedron Letters,2006,vol. 47,p. 6765 - 6768

22
[ 347-84-2 ]
(E)-1-(4-fluorophenyl)-2-phenylethanone oxime [ No CAS ]
[ 445411-74-5 ]

Reference： [1]Journal of the American Chemical Society,2002,vol. 124,p. 7640 - 7641

23
lead(IV) acetate [ No CAS ]
[ 347-84-2 ]
acetic acid 2-(4-fluoro-phenyl)-2-oxo-1-phenyl-ethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 1511 - 1517

24
[ 4747-15-3 ]
[ 460-00-4 ]
[ 347-84-2 ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 3122 - 3132

25
[ 347-84-2 ]
[ 3834-66-0 ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 15438 - 15441
[2]Tetrahedron Letters,2015,vol. 56,p. 1575 - 1580
[3]Chemistry of Heterocyclic Compounds,2006,vol. 42,p. 901 - 906
[4]European Journal of Medicinal Chemistry,2008,vol. 43,p. 2004 - 2010
[5]Synlett,2012,vol. 23,p. 1025 - 1030

26
[ 103-82-2 ]
[ 347-84-2 ]

Reference： [1]Chemistry of Heterocyclic Compounds,2006,vol. 42,p. 901 - 906
[2]Patent: CN103420823,2016,B
[3]Patent: CN106397296,2017,A

27
[ 347-84-2 ]
3-(4-fluorophenyl)-2-phenyl-6,7-dihydro-5H-1,4-diazepine [ No CAS ]

Reference： [1]Chemistry of Heterocyclic Compounds,2006,vol. 42,p. 901 - 906

28
[ 347-84-2 ]
4-[4-(4-fluoro-phenyl)-[1,2,3]thiadiazol-5-yl]-benzenesulfonyl chloride [ No CAS ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2005,vol. 180,p. 1593 - 1600

29
[ 347-84-2 ]
4-[4-(4-fluorophenyl)-1,2,3-thiadiazole-5-yl]benzensulfonamide [ No CAS ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2005,vol. 180,p. 1593 - 1600

30
[ 347-84-2 ]
[ 73424-52-9 ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2005,vol. 180,p. 1593 - 1600
[2]Chemische Berichte,1980,vol. 113,p. 183 - 192

31
[ 347-84-2 ]
[ 185345-83-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1881 - 1893

32
[ 347-84-2 ]
[ 699003-03-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1881 - 1893

33
[ 347-84-2 ]
[ 699003-16-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1881 - 1893

34
[ 347-84-2 ]
[ 699003-42-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1881 - 1893

35
[ 347-84-2 ]
[ 699003-39-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1881 - 1893

36
[ 347-84-2 ]
C₁₉H₁₅FN₃O₃S^(1-)*Na⁽¹⁺⁾ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1881 - 1893

37
[ 347-84-2 ]
α-benzamidylbenzyl p-fluorophenyl ketone [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2002,vol. 124,p. 7640 - 7641

38
[ 347-84-2 ]
α-benzamidylbenzyl p-fluorophenyl ketone [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2002,vol. 124,p. 7640 - 7641

39
[ 347-84-2 ]
2-(4-fluorophenyl)-5-isopropyl-3-phenyl-1H-pyrrole [ No CAS ]