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[ CAS No. 175278-09-8 ]

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CAS No. :	175278-09-8	MDL No. :	MFCD00179338
Formula :	C₇H₅BrF₃NO	Boiling Point :	209.2°C at 760 mmHg
Linear Structure Formula :	-	InChI Key :	-
M.W :	256.02 g/mol	Pubchem ID :	737382
Synonyms :

Safety of [ 175278-09-8 ]

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P280-P301+P310	UN#:	2810
Hazard Statements:	H301-H317-H412	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 175278-09-8 ]

Upstream synthesis route of [ 175278-09-8 ]
Downstream synthetic route of [ 175278-09-8 ]

[ 175278-09-8 ] Synthesis Path-Upstream 1~4

1
[ 175278-09-8 ]
[ 2252-44-0 ]

Reference： [1] Patent: WO2007/107820, 2007, A2, . Location in patent: Page/Page column 7

2
[ 1535-75-7 ]
[ 175278-09-8 ]

Reference： [1] Patent: WO2007/107820, 2007, A2, . Location in patent: Page/Page column 7

3
[ 67-56-1 ]
[ 175278-09-8 ]
[ 201230-82-2 ]
[ 457097-93-7 ]

Yield	Reaction Conditions	Operation in experiment
54%	at 100℃; for 36 h;	To a solution of 4-bromo-2-(trifluoromethoxy)aniline (10 g, 50.21 mmol) in methanol (150 mL) in a pressure tank reactor was added TEA (11.84 g, 117.01 mmol), Pd(dppf)Ci₂ CH₂Q₂ (2.4 g, 2.94 mmol). Then the reactor was charged with CO (g) (20 atm). The resulting reaction was stirred for 1.5 days at 100°C. Then it was diluted with water (200 mL), extracted with ethyl acetate (3 x 100 mL) and the organic layers combined and dried in an oven under reduced pressure. The resulting mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1 :50) to afford methyl 4- amino-3-(trifluoromethoxy)benzoate as yellow solid (5 g, 54percent).

Reference： [1] Patent: WO2014/66795, 2014, A1, . Location in patent: Paragraph 0175

4
[ 175278-09-8 ]
[ 886500-50-1 ]

Reference： [1] Patent: WO2014/66795, 2014, A1,

[ 175278-09-8 ] Synthesis Path-Downstream 1~25

1
[ 175278-09-8 ]
[ 87-13-8 ]
C₁₅H₁₅BrF₃NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 135℃; for 2h;	EXAMPLE 122 N-(4-Chlorobenzyl)-4-hydroxy-6-(3-hydroxy-1-propynyl)-8-(trifluoromethoxy)-3-quinolinecarboxamide [] A mixture of <strong>[175278-09-8]4-bromo-2-trifluoromethoxyaniline</strong> (10.0 g) and diethyl ethoxymethylenemalonate (7.9 mL) is heated to 135 C for 2 h. The reaction mixture is diluted with diphenylether (90 mL) and heated to reflux with removal of ethanol by a Dean-Start trap for 30 min. The resulting precipitate is poured into heptane and filtered to afford 10.83 g (73%) of the 6-bromo-8-trifluoromethoxyquinoline ethyl ester. A mixture of the quinoline ethyl ester (5.0 g) and 4-chlorobenzylamine (12.0 mL) are heated to 190 C for 1 h. The mixture is diluted with toluene (25 mL), allowed to cool to rt, and filtered. The crude product is recrystallized (HOAc, water) to afford 5.03 g (80%) of the amide. The resulting amide (469 mg), bis(triphenylphosphine)palladium (II) chloride (175 mg), and triethylamine (5.0 mL) are dissolved in DMF (50 mL). Propargyl alcohol (2.5 mL) is added over 20 h at 90 C. The reaction mixture was allowed to cool to rt, poured into aq. ammonium chloride (200 mL) and extracted with ethyl acetate (4 x 50 mL). The organic layer is washed with sat. aqueous brine (10 mL). The aqueous layer is back-extracted with ethyl acetate (20 mL). The combined organic layers are dried (MgSO4) and concentrated. The crude product is purified by column chromatography (dichloromethane/ methanol, 100/1; 50/1; 100/3) to afford 580 mg (26%) of the title compound as a white solid. Physical characteristics are as follows: Mp 262 C dec.1H NMR (DMSO-d6) delta 12.89, 10.12, 8.64, 8.20, 7.86, 7.42-7.34, 5.42, 4.55, 4.35.13C NMR (CF3CO2D) delta 175.7, 167.4, 144.1, 139.1, 134.8, 133.3, 131.5, 129.2, 129.1, 127.3, 126.3, 123.6, 123.2, 120.6, 107.3, 84.8, 84.1, 55.5, 44.1.IR (drift) 1936 (w), 1657 (s), 1602, 1574, 1544, 1517 (s), 1279 (s), 1268, 1223 (s), 1212 (s), 1183, 1161 (s), 1048, 1020, 802 cm-1.MS (ESI-) m/z 449 (M-H)-.Anal. Found for C21H14ClF3N2O4: C, 55.86; H, 3.16; N, 6.09; Cl, 7.96

Reference： [1]Patent: EP1042295,2005,B1 .Location in patent: Page/Page column 91-92

2
[ 175278-09-8 ]
[ 126747-14-6 ]
[ 885477-08-7 ]

Yield	Reaction Conditions	Operation in experiment
38%	With sodium carbonate;5%-palladium/activated carbon; In methanol; water; at 70℃; for 12h;	Step 1: A mixture of <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)benzenamine</strong> (512 mg, 2.0 mmol), 4-cyanophenylboronic acid (324 mg, 2.2 mmol), 5% activated palladium on carbon (50% wet, 100 mg) and sodium carbonate (424 mg, 4.0 mmol) in a mixture of methanol:water (20 mL, 1:1) was heated at 70 C. for 12 hours. The reaction mixture was filtered through a celite pad and the filtrate evaporated to give a crude residue. Purification on silica gel using a mixture of ethyl acetate:hexane (4:1) as eluant gave the light yellow solid 4-amino-3-trifluoromethoxy-biphenyl-4-carbonitrile (210 mg, 38% yield).

Reference： [1]Patent: US2006/94749,2006,A1 .Location in patent: Page/Page column 19; 20

3
[ 175278-09-8 ]
4-bromo-1-chloro-2-(trifluoromethyloxy)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%		NaNO2 (2.43 g, 0.035 mol) in water (10 mL) was added in portions over 30 min to <strong>[175278-09-8]4-bromo-2-trifluoromethoxyaniline</strong> (9 g, 35 mmol) in a mixture of HCl (aq, cone, 25 mL) and water (25 mL) at (0-2 0C). The mixture was stirred at 0-2 0C for 15 min and CuCl (6 g, 61 mmol) in HCl (aq, cone, 10 mL) was added dropwise. After 10 min at rt, the mixture was heated at reflux for 15 min. Steam-distillation followed by extraction (CH2Cl2), drying (Na2SO4) of the distillate followed by concentration and distillation (bp 82-84 0C at 20 Torr) gave 3.86 g (40%) of the sub-title compound.
40%		NaNO2 (2.43 g, 0.035 mol) in water (10 mL) was added in portions over 30 min to <strong>[175278-09-8]4-bromo-2-trifluoromethoxyaniline</strong> (9g, 35 mmol) in a mixture of HCl (aq, cone,25 mL) and water (25 mL) at (0-2 0C). The mixture was stirred at 0-2 0C for 15 min and CuCl (6 g, 61 mmol) in HCl (aq, cone, 10 mL) was added dropwise. After EPO <DP n="136"/>10 min at it, the mixture was heated at reflux for 15 min. Steam-distillation followed by extraction (CHoCl2), drying (Na2SO4) of the distillate followed by concentration and distillation (bp 82-840C at 20 Torrj gave 3.86 g (40%) of the sub-title compound.
	With copper dichloride; isopentyl nitrite; In acetonitrile; at 70℃; for 3h;	A mixture of isoamyl nitrite (4 mL, 30 mmol), copper (II) chloride (3.22 g, 24 mmol) and <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (Compound 30A) (5.1 g, 20 mmol) in acetonitrile (80 mL) was heated at 70 C for 3 hours. The mixture was poured into an aqueous HC1 solution (0.5 M, 50 mL) and extracted with ethyl acetate (50 mL x 2). The combined extracts were washed with water (50 mL x 4) and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with flash column chromatography on silica gel (petroleum ether) to afford Compound 30B. LC-MS (ESI) m/z: non-ionizable compound under routine conditions used. ?H-NIVIR (DMSO-d6, 400 IVII{z): 5 (ppm) 7.33-7.3 5 (m, 1H), 7.37-7.40 (m, 1H), 7.48 (t, J= 1.6 Hz, 1H).

Reference： [1]Patent: WO2006/77364,2006,A1 .Location in patent: Page/Page column 74
[2]Patent: WO2006/77367,2006,A1 .Location in patent: Page/Page column 134-135
[3]Patent: WO2019/133770,2019,A2 .Location in patent: Paragraph 00624; 00625; 00626

4
[ 175278-09-8 ]
[ 7447-39-4 ]
4-bromo-1-chloro-2-(trifluoromethyloxy)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tert.-butylnitrite; In acetonitrile;	EXAMPLE 23A 4-bromo-1-chloro-2-(trifluoromethoxy)benzene A mixture of tert-butyl nitrite (1.78 mL, 15.0 mmol), copper (II) chloride (1.61 g, 12.0 mmol) and <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (2.56 g, 10.0 mmol) in acetonitrile (40 mL) was heated to 70 C., stirred for 3 hours, cooled to room temperature, poured into 0.5M HCl, and extracted with diethyl ether. The combined extracts were washed with water and brine, dried (MgSO4), filtered, and concentrated to provide the desired product. MS (ESI(+)) m/e 275 (M+H)+.
	With tert.-butylnitrite; In acetonitrile;	Example 23A 4-bromo-1-chloro-2-(trifluoromethoxy)benzene A mixture of tert-butyl nitrite (1.78 mL, 15.0 mmol), copper (II) chloride (1.61 g, 12.0 mmol) and <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (2.56 g, 10.0 mmol) in acetonitrile (40 mL) was heated to 70 C., stirred for 3 hours, cooled to room temperature, poured into 0.5M HCl, and extracted with diethyl ether. The combined extracts were washed with water and brine, dried (MgSO4), filtered, and concentrated to provide the desired product. MS (ESI(+)) m/e 275 (M+H)+.

Reference： [1]Patent: US2002/55631,2002,A1
[2]Patent: US2002/86887,2002,A1

5
[ 175278-09-8 ]
[ 87-13-8 ]
[ 228728-40-3 ]

Yield	Reaction Conditions	Operation in experiment
10.83 g (73%)		EXAMPLE 122 N-(4-Chlorobenzyl)-4-hydroxy-6-(3-hydroxy-1-propynyl)-8-(trifluoromethoxy)-3-quinolinecarboxamide STR160 A mixture of <strong>[175278-09-8]4-bromo-2-trifluoromethoxyaniline</strong> (10.0 g) and diethyl ethoxymethylenemalonate (7.9 mL) is heated to 135 C. for 2 h. The reaction mixture is diluted with diphenylether (90 mL) and heated to reflux with removal of ethanol by a Dean-Start trap for 30 min. The resulting precipitate is poured into heptane and filtered to afford 10.83 g (73%) of the 6-bromo-8-trifluoromethoxyquinoline ethyl ester.

Reference： [1]Patent: US6093732,2000,A

6
[ 860617-71-6 ]
[ 175278-09-8 ]
5-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium fluoride;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In tetrahydrofuran; hexane; for 16h;	<strong>[175278-09-8]4-Bromo-2-(trifluoromethoxy)aniline</strong> (1.3 g, 5.0 mmol), 5-cyano-1-methyl-1H-pyrrol-2-yl boronic acid (0.9 g, 6.0 mmol), potassium fluoride (0.96 g, 16.5 mmol), and tris(dibenzylideneacetone)dipalladium (0.12 g, 0.12 mmol) were placed in an oven dried flask under nitrogen and THF (12.5 mL) was added. Tri-t-butylphosphine (10 wt % in hexane) (0.356 mL, 0.24 mol) was added and the reaction was stirred for 16 hours. The reaction mixture was filtered through silica, rinsed with ethyl acetate, and concentrated. The crude product was pre-adsorbed onto the Celite reagent and purified via Isco chromatography (the Redisep column, silica, gradient 5-30% ethyl acetate in hexane) to afford 1.0 g (71%) of 5-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile. HPLC purity 98.2% at 210-370 nm, 9.6 min.; the Xterra RP18 instrument, 3.5%, 150×4.6 mm column, 1.2 mL/min., 85/15-5/95 (Ammon. Form. Buff. PH=3.5/ACN+MeOH) for 10 min., hold 4 min. MS (ES) m/z 281.
71%	tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In tetrahydrofuran; hexane; for 16h;	Example 58 5-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile <strong>[175278-09-8]4-Bromo-2-(trifluoromethoxy)aniline</strong> (1.3 g, 5.0 mmol), 5-cyano-1-methyl -1H-pyrrol-2-ylboronic acid (0.9 g, 6.0 mmol), potassium fluoride (0.96 g, 16.5 mmol), and tris(dibenzylideneacetone)dipalladium (0.12 g, 0.12 mmol) were placed in an oven dried flask under nitrogen and THF (12.5 mL) was added. Tri-t-butylphosphine (10 wt % in hexane) (0.356 mL, 0.24 mol) was added and the reaction was stirred for 16 hours. The reaction mixture was filtered through silica, rinsed with ethyl acetate, and concentrated. The crude product was pre-adsorbed onto the Celite reagent and purified via Isco chromatography (the Redisep column, silica, gradient 5-30% ethyl acetate in hexane) to afford 1.0 g (71%) of 5-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile. HPLC purity 98.2% at 210-370 nm, 9.6 min.; the Xterra RP18 instrument, 3.5mu, 150*4.6 mm column, 1.2 mL/min., 85/15-5/95 (Ammon. Form. Buff. PH=3.5/ACN+MeOH) for 10 min., hold 4 min. MS (ES) m/z 281.

Reference： [1]Patent: US2007/27126,2007,A1 .Location in patent: Page/Page column 14
[2]Patent: US2007/27201,2007,A1 .Location in patent: Page/Page column 21
[3]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7119 - 7122

8
[ 175278-09-8 ]
[ 2252-44-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; sodium nitrite; In water; isopropyl alcohol;Product distribution / selectivity;	1b. Preparation of 1 -bromo-3-trifluoromethoxybenzene. 2579.53 g of 2-propanol and 1100 g of the product from stage Ia are placed in a 10 litre lined glass reactor with 4 necks and outlet on bottom, and a previously prepared solution of 382.52 g of NaNO2 in 766.18 g of water is added. 459.6 g of concentrated sulphuric acid are then metered slowly. The acids are diluted and the upper organic phase is separated from the lower aqueous phase. The organic phase is washed and a first organic phase and an upper aqueous phase are separated. The latter is further diluted with water until a second organic phase is released. This organic phase is added to the first and everything is washed again, separating an aqueous phase and an organic phase which, after being anhydrified with CaCl2, undergoes distillation to provide the product indicated in the title (final yield 84%). B.p. 156-158C/760 mmHg.

Reference： [1]Patent: WO2007/107820,2007,A2 .Location in patent: Page/Page column 7

9
[ 1535-75-7 ]
[ 175278-09-8 ]

Yield	Reaction Conditions	Operation in experiment
		1a. Preparation of 4-bromo-2-trifluoromethoxyaniline (formula (IIIa). 3462 g of acetic acid and 1700 g of 2-trifluoromethoxyaniline are placed at room temperature in a 10 1 lined glass reactor with 4 necks, outlet on bottom, thermostat with brine cryostat, provided with mechanical agitation, bubble condenser and thermometer; the mixture is subsequently cooled to 0-5C and 1894.26 g of NBS are added, maintaining the temperature at 0-50C. At the end of the reaction the mixture is brought back to room temperature and the acetic acid is eliminated by distillation. The residue is washed with water, the phases are separated, the organic phase is neutralised with NaHCCbeta and the phases are separated again, the inorganic phase is washed with water and the product indicated in the title is isolated. B.p. 115C/30 mmHg.
	With N-Bromosuccinimide; acetic acid; at 0 - 20℃;	To a solution of 2-(trifluoromethoxy)aniline (318A) (2.655 mg, 15 mmol) in acetic acid (6 mL) was added NBS (2.94 g, 16.5 mmol) at 0 C and stirred at room temperature overnight. It was concentrated under reduced pressure. The residue was diluted with ethyl acetate (100 mL), washed with water (30 mL) and brine (30 mL), dried over anhydrous sodium sulfate, concentrated, and purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 20% v/v) to afford Compound 318B. LC-MS (ESI) m/z: 256 [M +H]+; 'H-NMR (CDCb, 400 MHz): d (ppm) 3.89 (s, 2H), 6.67 (d, J= 8.8 Hz, 1H), 7.18 (dd, J= 8.8, 2.4 Hz, 1H), 7.28 (d, J= 2.4 Hz, 1H).

Reference： [1]Patent: WO2007/107820,2007,A2 .Location in patent: Page/Page column 7
[2]Patent: WO2019/133770,2019,A2 .Location in patent: Paragraph 001669; 001670; 001671

10
[ 109-01-3 ]
[ 175278-09-8 ]
[ 1034732-96-1 ]

Yield	Reaction Conditions	Operation in experiment
70%	With lithium hexamethyldisilazane; DavePhos;tris-(dibenzylideneacetone)dipalladium(0); In tetrahydrofuran; for 1h;Inert atmosphere; Reflux;	Tris(dibenzilideneacetone)dipalladium (1.1 g, 1.2 mmol), 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)-biphenyl (0.94 g, 2.4 mmol), <strong>[175278-09-8]4-bromo-2-trifluoromethoxy-phenylamine</strong> (30.7 g, 120 mmol) in THF (50 mL) were charged in a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. LiN(TMS)2 solution (1 M in THF, 288 mL) and N-methylpiperazine (26.7 mL, 194 mmol) were added and the reaction refluxed for 1 h. The reaction mixture was then allowed to cool to room temperature and filtered through a pad of celite. The organic phase was concentrated, the residue dissolved in DCM (200 ml) and washed with water (1 x 100 ml). The organic phases were dried over anhydrous Na?SCM, the solvent evaporated in vacuo and the crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10) to afford 23 g of 4-(4-methyl-piperazin-1-yl)-2- trifluoromethoxy-phenylamine (70% yield) as a light brown powder. MS calc: 276.1318; MS found: 276.1320

Reference： [1]Patent: WO2010/108921,2010,A1 .Location in patent: Page/Page column 43

11
[ 175278-09-8 ]
[ 1352342-49-4 ]

Reference： [1]Patent: WO2011/156610,2011,A2

12
[ 175278-09-8 ]
[ 1352338-53-4 ]

Reference： [1]Patent: WO2011/156610,2011,A2

13
[ 175278-09-8 ]
[ 1352338-54-5 ]

Reference： [1]Patent: WO2011/156610,2011,A2

14
[ 175278-09-8 ]
[ 762-21-0 ]
[ 1352342-47-2 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; for 5h;Reflux;	4-Bromo-2-trifluoromethoxy-phenylamine (13 g, 0.05 mol) and But-2-ynedioic acid diethyl ester (10.3 g, 0.12 mol) were dissolved in EtOH (120ml) in a 500 ml round bottom flask and refluxed. The reaction was monitored by LC-MS. 3 h later; 0.3 eq. but-2-ynedioic acid diethyl ester was added. At t = 5h, the reaction mixture was concentrated down to remove the solvent under vacuum, a thick oil was obtained and was used without purification for the next step. MS [M+H]+ = 426.

Reference： [1]Patent: WO2011/156610,2011,A2 .Location in patent: Page/Page column 156; 157

15
[ 175278-09-8 ]
[ 762-21-0 ]
[ 1352342-48-3 ]

Reference： [1]Patent: WO2011/156610,2011,A2

16
[ 75-15-0 ]
[ 175278-09-8 ]
C₁₅H₈Br₂F₆N₂O₂S₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 235 - 239

17
[ 175278-09-8 ]
[ 100-39-0 ]
[ 1386950-85-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetonitrile; for 20h;Reflux;	EXAMPLE 647-(2,6-dichlorobenzyl)-5-{ [4-^iperazin- l -yl)-2-(trifluoromethoxy)phenyl]amino}pyrido[3,4- d]pyridazin-4-ol EXAMPLE 64A /V,N-dibenzyl-<strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> To a mixture of <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (5 g. 19.53 mmol) and potassium carbonate (8.09 g, 58.89 mmol) in acetonitrile (200 mL) was added (bromomethyl)benzene (6.96 mL, 58.59 mmol) and the mixture was refluxed for 20 hours. The mixture was filtered and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel (200-300 mesh) eluting with 5/1 petroleum ether/ethyl acetate to give the title compound. MS : 436 (M + H+).
	With potassium carbonate; In acetonitrile; for 20h;Reflux;	Example 45 4-(2,6-dichlorobenzyl)-6-{ [4-(piperazin-l -yl)-2-(trifluoromethoxy)phenyl]amino }- lH- imidazo\|4,5-c]pyridine-7-carboxamide EXAMPLE 45A NN-dibenzyl-<strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> To a mixture of <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (5 g, 19.53 mmol) and potassium carbonate (8.09 g, 58.89 mmol) in acetonitrile (200 mL) was added(bromomethyl)benzene (6.96 mL, 58.59 mmol) and the mixture was refluxed for 20 hours. The mixture was filtered and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel (200-300 mesh) eluting with 5/1 petroleum ether/ethyl acetate to give the title compound. MS: 436 (M + H+).

Reference： [1]Patent: WO2012/97682,2012,A1 .Location in patent: Page/Page column 121
[2]Patent: WO2012/97684,2012,A1 .Location in patent: Page/Page column 98

18
[ 175278-09-8 ]
[ 1386950-86-2 ]

Reference： [1]Patent: WO2012/97682,2012,A1

19
[ 175278-09-8 ]
[ 1374641-77-6 ]

Reference： [1]Patent: WO2012/97682,2012,A1

20
[ 175278-09-8 ]
[ 1489391-85-6 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2013,vol. 61,p. 10858 - 10863

21
[ 175278-09-8 ]
[ 1489176-06-8 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2013,vol. 61,p. 10858 - 10863

22
[ 175278-09-8 ]
[ 1489176-75-1 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2013,vol. 61,p. 10858 - 10863

23
[ 175278-09-8 ]
[ 97-51-8 ]
[ 1577131-71-5 ]

Yield	Reaction Conditions	Operation in experiment
35%	In ethanol; for 1h;Reflux;	The title compound, (E)-2-(((4-bromo-2-(trifluoromethoxy)phenyl)imino)methyl)-4-nitrophenol, was prepared by reflux a mixture of a solution containing 2-hydroxy-5-nitrobenzaldehyde (0.0138 g, 0.082 mmol) in 20 ml ethanol and a solution containing <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (0.0211 g, 0.082 mmol) in 20 ml ethanol. The reaction mixture was stirred for 1 hunder reflux. The crystals of suitable for (E)-2-(((4-bromo-2-(trifluoromethoxy)phenyl)imino)methyl)-4-nitrophenol X-ray analysis were obtained from ethyl alcohol by slow evaporation (yield%35; m.p 198-200 C).

Reference： [1]Journal of Molecular Structure,2014,vol. 1063,p. 295 - 306

24
[ 67-56-1 ]
[ 175278-09-8 ]
[ 201230-82-2 ]
[ 457097-93-7 ]

Yield	Reaction Conditions	Operation in experiment
54%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triethylamine; at 100℃; under 15201.0 Torr; for 36h;	To a solution of <strong>[175278-09-8]4-bromo-2-(trifluoromethoxy)aniline</strong> (10 g, 50.21 mmol) in methanol (150 mL) in a pressure tank reactor was added TEA (11.84 g, 117.01 mmol), Pd(dppf)Ci2 CH2Q2 (2.4 g, 2.94 mmol). Then the reactor was charged with CO (g) (20 atm). The resulting reaction was stirred for 1.5 days at 100C. Then it was diluted with water (200 mL), extracted with ethyl acetate (3 x 100 mL) and the organic layers combined and dried in an oven under reduced pressure. The resulting mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1 :50) to afford methyl 4- amino-3-(trifluoromethoxy)benzoate as yellow solid (5 g, 54%).

Reference： [1]Patent: WO2014/66795,2014,A1 .Location in patent: Paragraph 0175

25
[ 175278-09-8 ]
[ 1261444-00-1 ]

Reference： [1]Patent: WO2014/66795,2014,A1

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Precautionary Statements-General
Code	Phrase
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Prevention
Code	Phrase
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P321
P322
P330	Rinse mouth.
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P378
P380	Evacuate area.
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P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
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Code	Phrase
P401
P402	Store in a dry place.
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Code	Phrase
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H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
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H240	Heating may cause an explosion
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H261	In contact with water releases flammable gas
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H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere