[ CAS No. 168971-68-4 ] {[proInfo.proName]}

Name: 168971-68-4|1-Bromo-2-fluoro-4-(trifluoromethoxy)benzene|98%
Brand: Ambeed
SKU: A175622
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Quality Control of [ 168971-68-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 168971-68-4 ]

Product Details of [ 168971-68-4 ]

CAS No. :	168971-68-4	MDL No. :	MFCD06657548
Formula :	C₇H₃BrF₄O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KZMHSGBETSENAT-UHFFFAOYSA-N
M.W :	259.00	Pubchem ID :	22065211
Synonyms :

Calculated chemistry of [ 168971-68-4 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	2
Num. H-bond acceptors :	5.0
Num. H-bond donors :	0.0
Molar Refractivity :	40.78
TPSA :	9.23 Å²

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) :	-5.12 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.4
Log Po/w (XLOGP3) :	3.89
Log Po/w (WLOGP) :	5.17
Log Po/w (MLOGP) :	3.44
Log Po/w (SILICOS-IT) :	3.51
Consensus Log Po/w :	3.68

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.11
Solubility :	0.0203 mg/ml ; 0.0000783 mol/l
Class :	Moderately soluble
Log S (Ali) :	-3.78
Solubility :	0.0428 mg/ml ; 0.000165 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.16
Solubility :	0.018 mg/ml ; 0.0000693 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.87

Safety of [ 168971-68-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362+P364-P403+P233-P501	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 168971-68-4 ]

* 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 [ 168971-68-4 ]

[ 168971-68-4 ] Synthesis Path-Downstream 1~55

1
[ 168971-68-4 ]
[ 5419-55-6 ]
[ 503309-10-2 ]

Yield	Reaction Conditions	Operation in experiment
41%	With hydrogenchloride; n-butyllithium; In tetrahydrofuran;	Example I 2-Fluoro-4-trifluoromethoxybenzeneboronic Acid To a solution of n-butyllithium (2.5 M solution in hexanes, 14.1 mL) in THF (30 mL) at -98 C. was added a solution of <strong>[168971-68-4]4-bromo-3-fluorotrifluoromethoxy-benzene</strong> in THF (3 mL). After stirring for 10 min. at -98 C., triisopropyl borate (4.88 mL, 3.98 g, 21 mmol) was added at a rate needed to keep the temperature below -97 C. The reaction mixture was allowed to warm to -30 C. over 30 minutes, re-cooled to -78 C. and stirred at this temperature for 30 min. Concentrated hydrochloric acid (2 mL) was added and the reaction mixture was concentrated under reduced pressure. Dilute hydrochloric acid (0.2 N, 15 mL) was added and the mixture was extracted with ether (320 mL). The combined ethereal layers were extracted with dilute sodium hydroxide (0.02 N, 330 mL). The combined aqueous extracts were cooled to 0 C., acidified to pH 3.5 using concentrated hydrochloric acid and extracted with ether (3*30 mL). The combined ethereal layers were then washed with water (15 mL) and brine (15 mL), dried over magnesium sulphate and concentrated under reduced pressure to leave 2.3 g of yellow solid. Recrystallisation from hexane afforded pink needles (1.25 g, 41%): mp 89-93 C.; 1H NMR (CDCl3) delta 7.89 (t, 1H), 7.07 (d, 1H), 6.94 (d, 1H), 5.11 (d, 2H); EI/MS 223 m/e (M-1).
43 g	With n-butyllithium; In tetrahydrofuran; toluene; at -78 - -70℃; for 4h;	Tripropan-2-yl borate (43.6 g, 232 mmol) was added to a solution of <strong>[168971-68-4]4-bromo-3-fluorophenyl trifluoromethyl ether</strong> (50.0 g, 193 mmol) in toluene (400 mL) and tetrahydrofuran (100 mL), and the mixture was cooled to -78 C. n-Butyllithium (2.5 M solution; 92.7 mL, 232 mmol) was then added drop-wise, at a rate that maintained the reaction temperature below -60 C., and the reaction mixture was stirred at -70 C. for 4 hours. After the reaction mixture had been warmed to -20 C., it was quenched via addition of aqueous hydrochloric acid (2 M, 200 mL), and then stirred at room temperature (20 C.) for 40 minutes. The aqueous layer was extracted with ethyl acetate (3×50 mL), and the combined organic layers were washed with saturated aqueous sodium chloride solution (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford the product (43 g) as a white solid, which was carried directly to the next step.

Reference： [1]Patent: US2003/134748,2003,A1
[2]Patent: US2016/222007,2016,A1 .Location in patent: Paragraph 0330; 0331

2
[ 168971-68-4 ]
[ 73183-34-3 ]
[ 1073477-73-2 ]

Yield	Reaction Conditions	Operation in experiment
61.4%	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 80℃; for 15h;	1-Bromo-2-fluoro-4-(trifluoromethoxy)benzene (7.41 g, 28.61 mmol) was dissolved in DMSO (50 mL). 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (8.43 g, 33.19 mmol), PdCl2 (dppf) (1.035 g, 1.43 mmol) and potassium acetate (5.62 g, 57.22 mmol) were added and the mixture was heated in an oil bath at 80 C. for 15 h. The reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over Na2SO4 and evaporated. The residue was purified by automated flash chromatography on a BiotageKP-SIL 340 g column. A gradient from 0% to 25% of EtOAc in heptane over 10 CV was used as mobile phase. 2-(2-Fluoro-4-(trifluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.38 g, 61.4%) was obtained as colorless solid.
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 2h;Inert atmosphere; Microwave irradiation;	Step A: Preparation of 2-(2-fluoro-4-(trifluoromethoxy)phenyl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane. To a microwave vial equipped with a magnetic stir bar were added 4,4,4',4',5,5,5',5'-octamethyl- 2,2'-bi(l,3,2-dioxaborolane) (294 mg, 1.16 mmol), potassium acetate (KOAc; 189 mg, 1.93 mmol) and Pd(dppf)Ci2 (70.6 mg, 0.097 mmol) and the vial was purged with N2. The resulting mixture was treated with a solution of l-bromo-2-fluoro-4-(trifluoromethoxy)benzene (250 mg, 0.96 mmol) in 1,4-dioxane (3.9 mL). The reaction vessel was capped, placed in a Biotage Initiator microwave reactor for 2 h at 100 C, with external IR-sensor temperature monitoring from the side of the vessel. The cooled reaction mixture was filtered through a pad of Celite rinsing with EtOAc, and the filtrate was washed with sat'd aq NaHC03 (15 mL) and brine (2 x 15 mL). The organic phase was dried over MgS04, filtered, and concentrated to a brown oil which was used without further purification: 1H NMR (400 MHz, CDC13) delta 7.77 (dd, J= 8.3, 6.8 Hz, 1H), 7.01 (ddd, J= 8.3, 2.3, 1.1 Hz, 1H), 6.92 (ddd, J= 9.6, 2.2, 1.0 Hz, 1H), 1.36 (s, 12H); EIMS mlz 306.
1.29 g	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 16h;	A mixture of A-32 (1.25 g, 4.83 mmol), 4,4,5,5-tetramethyl-2-(4,4,5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (3.68 g, 14.48 mmol), Pd(dppf)Cl2.CH2Cl2 (394.13 mg, 482.63 mmol) and KOAc (947.30 mg, 9.65 mmol) in dioxane (30 mL) was stirred at 90 C for 16 hours. After cooling to room temperature, the mixture was diluted with EtOAc (50 mL), filtered through silica gel, and concentrated to give a residue that was purified by flash chromatography on silica gel (EtOAc in PE = 0% to 1%) to afford A-32 (1.29 g) as an oil. H NMR (400MHz CDC13) _ = 7.78 (dd, 1H), 7.01 (d, 1H), 6.93 (d, 1H), 1.37 (s, 12H).

With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 100℃; for 4h;

Example 106Preparation of Compound 416CF3Step A - synthesis of compound 206BCompound 206A (2.14 g, 8.3 mmol) was combined with PdCl2(dppf) (0.20 g, 0.25 mmol), bis(pinicolato)diboron (2.52 g, 9.9 mmol), and KOAc (2.43 g, 24 mmol) in DMSO (10 mL). The mixture was put under N2 atmosphere, heated to 1000C and allowed to stir at this temperature for 4 hours, then partitioned with water and 1 : 1 EtOAc/hexane. The organic phase was dried (MgSO4) and concentrated in vacuo, and the resulting residue was purified using flash column chromatography on silica (10% EtOAc/hexane) to provide compound 206B as a white solid.

Reference： [1]Patent: US2010/261755,2010,A1 .Location in patent: Page/Page column 26
[2]Patent: WO2015/160665,2015,A1 .Location in patent: Paragraph 00197
[3]Patent: WO2018/98499,2018,A1 .Location in patent: Page/Page column 138-139
[4]Patent: WO2008/130581,2008,A1 .Location in patent: Page/Page column 216

3
[ 168971-68-4 ]
[ 59016-93-2 ]
[ 1198422-71-7 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 282 - 294

4
[ 168971-68-4 ]
[ 123572-58-7 ]

Yield	Reaction Conditions	Operation in experiment
85%		Reference Example 1432-Fluoro-4-(trifluoromethoxy)aniline A mixture of <strong>[168971-68-4]4-bromo-3-fluoro(trifluoromethoxy)benzene</strong> (6.6 g, 26 mmol), benzophenone imine (6.4 mL, 38 mmol), Pd2(dba)3 (0.58 g, 0.64 mmol), Xantphos (1.5 g, 2.6 mmol) and sodium tert-butoxide (3.7 g, 38 mmol) in 1,4-dioxane (120 mL) was stirred at 100 C. under N2 atmosphere for 5 h. After stirring at room temperature overnight, the mixture was concentrated under reduced pressure. The residue was partitioned between AcOEt and water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was chromatographed on silica gel (0/100-5/95 AcOEt/hexane) to give a yellow oil. The residual oil was dissolved in THF (150 mL), and 1 M HCl aqueous solution (50 mL) was added to the mixture. After stirring at room temperature for 1 h, the mixture was basified with 8 M NaOH aqueous solution and extracted with diethyl ether. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was chromatographed on silica gel (0/100-5/95 AcOEt/hexane) to give the title compound (4.2 g, 85% yield) as a pale yellow oil: 1H NMR (300 MHz, DMSO-d6): delta ppm 5.36 (2H, s), 6.75-6.85 (1H, m), 6.89-6.94 (1H, m), 7.12 (1H, dd, J=11.7, 2.3 Hz).
30%		A mixture of <strong>[168971-68-4]1-bromo-2-fluoro-4-(trifluoromethoxy)benzene</strong> Int-172-38 (12.8 g, 49.4 mmol), benzophenone imine (10 mL, 59.3 mmol), Pd2(dba)3 (1.1 g, 1.23 mmol), XantPhos (2.8 g, 4.9 mmol) and NaOtBu (5.7 g, 59.3 mmol) in 1,4-dioxane (100 mL) was stirred and heated at 100 C overnight. After cooling to room temperature, the mixture was concentrated. The residue was then partitioned between EtOAc and H2O, and the organic layer was separated, dried over Na2SO4 and concentrated. The residue was purified by column chromatography using hexanes/EtOAc (0 to 5% EtOAc in hexanes). The product was dissolved in THF (100 mL), and 1M aqueous HCl (50 mL) was added. After being stirred at room temperature for 1h, the mixture was partitioned between EtOAc and H2O. The organic layer was separated, washed with brine, dried over Na2SO4 and concentrated. The residue was purified by column chromatography using hexanes/EtOAc (0 to 20% EtOAc in hexanes). The product 30 was obtained as pale brown oil in 30% yield (5.4 mg). LCMS: (M+1) m/z = 196.

Reference： [1]Patent: US2010/197651,2010,A1 .Location in patent: Page/Page column 77
[2]Patent: WO2018/170492,2018,A1 .Location in patent: Page/Page column 191; 195; 198

5
[ 168971-68-4 ]
[ 503309-10-2 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 8421 - 8439

6
[ 168971-68-4 ]
[ 1574119-23-5 ]
[ 1574116-83-8 ]

Yield	Reaction Conditions	Operation in experiment
66.8%	With bis(tri-t-butylphosphine)palladium(0); lithium hydroxide; In N,N-dimethyl-formamide; at 80℃; for 1h;Inert atmosphere; Microwave irradiation;	Step 3: (1-benzyl-3-(2-fluoro-4-(trifluoromethoxy)phenyl)-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone (SC-262) Under an nitrogen atmosphere (1-benzyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone (50 mg, 0.106 mmol) was dissolved in DMF (0.5 mL) and LiOH (2 mg, 0.106 mmol), bis(tri-tert-butylphosphine)palladium (0) (3 mg, 0.007 mmol) and <strong>[168971-68-4]1-bromo-2-fluoro-4-(trifluoromethoxy)benzene</strong> (24 mg, 0.096 mmol) were subsequently added. The reaction mixture was stirred at 80 C. under microwave irridation for 1 h. The mixture was cooled to RT and the reaction was stopped by addition of 1M NaOH solution (2 mL). The crude product was extracted with EtOAc (23 mL) and the combined organic layers were washed with water (31 mL), dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The crude mass was purified by flash chromatography to give SC-262 (34 mg, 66.8%).
66.8%	With bis(tri-t-butylphosphine)palladium(0); lithium hydroxide; In N,N-dimethyl-formamide; at 80℃; for 1h;Inert atmosphere; Microwave irradiation;	Step 3: (1 -benzyl-3-(2-fluoro-4-(trifluoromethoxy)phenyl)-4-methyl-5-(trifluoromethyl)-1 H-pyrrol2-yl)(morpholino)methanone (SC-262)Under an nitrogen atmosphere (1 -benzyl-4-methyl-3-(4,4,5, 5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-5- (trifluoromethyl)-IH-pyrrol-2-yl)(morpholino)methanone (50 mg, 0.106 mmol) was dissolved in DMF (0.5 mL) and LiOH (2 mg, 0.106 mmol), bis(tri-tert-butylphosphine)palladium (0) (3 mg, 0.007 mmol) and <strong>[168971-68-4]1-bromo-2-fluoro-4-(trifluoromethoxy)benzene</strong> (24 mg, 0.096 mmol) were subsequently added. The reaction mixture was stirred at 80C under microwave irridation for I h. The mixture was cooled to RT and the reaction was stopped by addition of 1 M NaOH solution (2 mL). The crude product was extracted with EtOAc (2x3 mL) and the combined organic layers were washed with water (3x1 mL), dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The crude mass was purified by flash chromatography to give SC-262 (34 mg, 66.8 %).

Reference： [1]Patent: US2014/66426,2014,A1 .Location in patent: Paragraph 0804
[2]Patent: WO2014/32801,2014,A1 .Location in patent: Page/Page column 165

7
[ 168971-68-4 ]
[ 78191-00-1 ]
1-(2-fluoro-4-(trifluoromethoxy)phenyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%		n-Butyl lithium (6.17 mL, 9.87 mmol) was added drop-wise at -78 C. to a solution of <strong>[168971-68-4]1-bromo-2-fluoro-4-(trifluoromethoxy)benzene</strong> (2.13 g, 8.22 mmol) in diethyl ether (16.5 mL). The reaction was stirred for 30 minutes before drop-wise addition of N-methoxy-N-methylacetamide (1.272 g, 12.34 mmol). The reaction was stirred for 5 minutes at -78 C. then warmed to room temperature and stirred for 30 minutes. The solution was quenched with saturated NH4Cl, extracted with EtOAc, dried with Na2SO4, filtered, and concentrated under reduced pressure. Purification by flash silica gel chromatography, eluting with 10% EtOAc in heptanes provided 1-(2-fluoro-4-(trifluoromethoxy)phenyl)ethanone as a clear oil (1.118 g, 61%)

Reference： [1]Patent: US2016/145218,2016,A1 .Location in patent: Paragraph 0217

8
[ 168971-68-4 ]
(S)-N-((S)-1-(2-fluoro-4-(trifluoromethoxy)phenyl)ethyl)-2-methylpropane-2-sulfinamide [ No CAS ]

Reference： [1]Patent: US2016/145218,2016,A1

9
[ 168971-68-4 ]
(S)-1-(2-fluoro-4-(trifluoromethoxy)phenyl)ethanamine hydrochloride [ No CAS ]

Reference： [1]Patent: US2016/145218,2016,A1

10
[ 168971-68-4 ]
[ 1073477-74-3 ]

Reference： [1]Patent: US2016/222007,2016,A1
[2]Patent: WO2008/130581,2008,A1

11
[ 168971-68-4 ]
2-fluoro-6-iodo-4-(trifluoromethoxy)phenol [ No CAS ]

Reference： [1]Patent: US2016/222007,2016,A1

12
[ 168971-68-4 ]
2-[(benzyloxy)methoxy]-1-fluoro-3-iodo-5-(trifluoromethoxy)benzene [ No CAS ]

Reference： [1]Patent: US2016/222007,2016,A1

13
[ 168971-68-4 ]
2-[(benzyloxy)methoxy]-1-fluoro-3-(prop-1-yn-1-yl)-5-(trifluoromethoxy)benzene [ No CAS ]

Reference： [1]Patent: US2016/222007,2016,A1

14
[ 168971-68-4 ]
3-[(benzyloxy)methyl]-7-fluoro-2-methyl-5-(trifluoromethoxy)-1-benzofuran [ No CAS ]

Reference： [1]Patent: US2016/222007,2016,A1

15
[ 168971-68-4 ]
[7-fluoro-2-methyl-5-(trifluoromethoxy)-1-benzofuran-3-yl]methanol [ No CAS ]

Reference： [1]Patent: US2016/222007,2016,A1

16
[ 168971-68-4 ]
[3-fluoro-1a-methyl-5-(trifluoromethoxy)-1,1a-dihydro-6bH-cyclopropa[b][1]benzofuran-6b-yl]methanol [ No CAS ]

Reference： [1]Patent: US2016/222007,2016,A1

17
[ 168971-68-4 ]
2-[3-fluoro-1a-methyl-5-(trifluoromethoxy)-1,1a-dihydro-6bH-cyclopropa[b][1]benzofuran-6b-yl]methyl}-1H-isoindole-1,3(2H)-dione [ No CAS ]

Reference： [1]Patent: US2016/222007,2016,A1

18
[ 168971-68-4 ]
1-[3-fluoro-1a-methyl-5-(trifluoromethoxy)-1,1a-dihydro-6bH-cyclopropa[b][1]benzofuran-6b-yl]methanamine [ No CAS ]

Reference： [1]Patent: US2016/222007,2016,A1

19
[ 168971-68-4 ]
2-[3-fluoro-1a-methyl-5-(trifluoromethoxy)-1,1a-dihydro-6bH-cyclopropa[b][1]benzofuran-6b-yl]methyl}-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione [ No CAS ]

Reference： [1]Patent: US2016/222007,2016,A1

20
[ 168971-68-4 ]
3-amino-5-(2-fluoro-4-trifluoromethoxybenzenesulfonyl)pyridine-2-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2016/193812,2016,A1

21
[ 168971-68-4 ]
(3-amino-5-[2-fluoro-4-(trifluoromethoxy)phenyl]sulfonyl}pyridin-2-yl)(3-hydroxyazetidin-1-yl)methanone [ No CAS ]

Reference： [1]Patent: WO2016/193812,2016,A1

22
[ 168971-68-4 ]
3-amino-5-(2-fluoro-4-trifluoromethoxyphenylsulfanyl)pyridine-2-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Patent: WO2016/193812,2016,A1

23
[ 168971-68-4 ]
3-amino-5-(2-fluoro-4-trifluoromethoxyphenylsulfanyl)pyridine-2-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2016/193812,2016,A1

24
[ 168971-68-4 ]
[ 50448-95-8 ]
3-(2-fluoro-4-trifluoromethoxyphenylsulfanyl)propionic acid 2-ethylhexyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tris-(dibenzylideneacetone)dipalladium(0); N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In toluene; at 110℃;Inert atmosphere;	1-Bromo-2-fluoro-4-(trifluoromethoxy)benzene (CAS: 168971-68-4, 20 g, 77 mmol) was mixed with N,N-diisopropylethylamine (27 mL, 144 mmol) in toluene (260 mL). The mixture was flushed with N2. Next, Pd2(dba)3 (2.12 g, 2.32 mmol), Xantphos (2.68 g, 4.64 mmol) and 3-mercaptopropionic acid 2-ethylhexylester (CAS: 50448-95-8, 20 g, 77 mmol) were added. The mixture was flushed again with N2 and heated at 110 C overnight. The mixture was then filtered through a plug of silica and eluted with EtOAc. The combined organic fractions were concentrated, and the obtained residue was purified by column chromatography (a gradient from 100% petroleum ether to 5% EtOAc in petroleum ether was applied) to give the titled compound.

Reference： [1]Patent: WO2016/193812,2016,A1 .Location in patent: Paragraph 00277

25
[ 168971-68-4 ]
1-(2-fluoro-4-(trifluoromethoxy)phenyl)-N-hydroxypropan-1-imine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 7677 - 7702

26
[ 168971-68-4 ]
1-(2-fluoro-4-(trifluoromethoxy)phenyl)propan-1-amine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 7677 - 7702

27
[ 557-21-1 ]
[ 168971-68-4 ]
2-fluoro-4-(trifluoromethoxy)benzonitrile [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 7677 - 7702

28
[ 168971-68-4 ]
2-(3-bromo-5-(difluoromethyl)-4-fluorophenoxy)pyridine [ No CAS ]