Name: 17332-11-5|2-Bromo-4-methoxyphenol|97%
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[ 150-76-5 ]
[ 17332-11-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With bromine In dichloromethane
100%	With benzyltriphenylphosphonium peroxodisulfate; potassium bromide In acetonitrile for 4.5h; Heating;
100%	With bromine In dichloromethane at 0 - 20℃;

100%	With bromine In dichloromethane Inert atmosphere;
100%	With bromine In chloroform at 0 - 20℃; for 2h;	2.35.A 2-bromo-4-methoxyphenol To a solution of 4-methoxyphenol (10 g, 81 mmol) in CHC13 (50 mL) was added BR (4 mL, 78 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 h, then allowed to warm to room temperature, the mixture was stirred at room temperature for 1 h. The resulting mixture was diluted with dichloromethane (500 mL) and washed with saturated NaHS03 (3x 100 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (16.6 g, 100%) as an off- white solid which was used in the next step.
100%	With bromine In chloroform at 0 - 20℃; for 2h;	1.A Step A: 2-bromo-4-methoxyphenol To a solution of 4-methoxyphenol (10 g, 81 mmol) in CHC13 (50 mL) was added Br2(4 mL, 78 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 h, then allowed to warm to room temperature, the mixture was stirred at room temperature for 1 h. The resulting mixture was diluted with dichloromethane (500 mL) and washed with saturated NaHS03 (3 χ 100 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (16.6 g, 100%) as an off- white solid which was used in the next step.
100%	With bromine In chloroform at 0 - 20℃; for 2h;	2.A 2-bromo-4-methoxyphenol To a solution of 4-methoxyphenol (10 g, 81 mmol) in CHCl3 (50 mL) was added BR2(4 mL, 78 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h, then allowed to warm to room temperature, the mixture was stirred at room temperature for 1 h. The resulting mixture was diluted with dichloromethane (500 mL) and washed with saturated NaHSO3 (3×100 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (16.6 g, 100%) as an off-white solid which was used in the next step.
100%	With bromine In dichloromethane at 40℃; for 1h; Cooling with ice;	2.1 Step 1: Example 2b To a solution of Example 2a (51.2 g, 0.41 mol) in DCM (0.5 L) cooled in an ice bath was added Br2 (66 g, 0.41 mol) dropwise. After addition, the resulting solution was stirred at 40 °C for 1 h. The reaction mixture was washed with water (400 mL*3), NaHC03 (200 mL) and brine, dried over Na2S04 and concentrated to give the desired product (Example 2b, 86.1 g, yield 100%) as colorless oil, which was used in the next step without further purification.
100%	With bromine In chloroform at 0 - 20℃; for 1h;	2 Step A: 2-Bromo-4-methoxyphenol Br2 (4 mL, 78 mmol) was added to 4-methoxyphenol (10 g, 81 mmol) in CHCl3 (50 mL) at 0°C.The mixture was stirred at 0°C for 1 hour, and then the mixture was warmed to room temperature and stirred at room temperature for 1 hour.The final mixture was diluted in dichloromethane (500mL) and washed with saturated NaHSO3 (3×100mL) and saturated brine (200mL), dried over anhydrous sodium sulfate, filtered and concentrated to obtain the target compound (16.6g, 100%), which was off-white The solid was used directly in the next reaction.
99%	With bromine In chloroform at 25℃; for 0.25h;
98%	With 1-butyl-3-methylpyridinium tribromide at 20℃; for 0.2h;
98.7%	With bromine In dichloromethane for 2h; Cooling with ice;	2-Bromo-4-methoxyphenol (3) Br2 (64.7 g, 403 mmol) dissolved in CH2Cl2 (30 mL) was slowly addeddropwise to a solution of p-methoxyphenol (2) (50 g, 403 mmol) in CH2Cl2 (200 mL) under the ice bath.The reaction mixture was stirred for 2 h then poured into ice water and extracted with CH2Cl2. Theorganic layer was washed with a solution of saturated aqueous NaHCO3 and NaCl in sequence and thendried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure and the residue wassubjected to flash column chromatography (petroleum ether: EtOAc, 20:1, V/V) to give 3 (80.0 g, 98.7%)as colourless solid
97%	With bromine In dichloromethane at 0 - 20℃; for 2h;
97%	With bromine In dichloromethane at 0 - 20℃; for 1.5h;
96%	With 1,4-bis(3-methylimidazolium-1-yl)butane ditribromide In acetonitrile at 20℃; for 0.166667h; Green chemistry; regioselective reaction;
95%	With N-benzyl-N,N-dimethyl anilinium peroxodisulfate; potassium bromide In acetonitrile for 4.5h; Reflux; regioselective reaction;
95%	With N-Bromosuccinimide In acetonitrile at 0 - 20℃; for 3h;
93%	With o-xylylene bis(triethylammonium tribromide) In acetonitrile at 20℃; for 0.0833333h; regioselective reaction;	3.3. General Procedure for Bromination of AromaticCompounds General procedure: To a magnetic solution of aromatic compound (1 mmol)in acetonitrile (5 mL), OXBTEATB (0.233 g, 0.5 mmol) wasadded and stirred at room temperature for the appropriatetime (Table 1). The reaction was monitored by TLC (eluent:n-hexane/ethyl acetate: 5/1). The reaction mixture was transferredinto a separatory funnel after filtration of OXBTEABand was extracted with water (15 mL) and dichloromethane(20 mL). The organic layer was dried over anhydrousNa2SO4, and the solvent was concentrated in a rotary evaporator.The crude product was purified by passing it over acolumn of silica gel using a mixture of n-hexane and ethylacetate as the eluent. In order to regenerate the reagent, whitesolid was treated with liquid bromine. All the product structureswere confirmed by comparison of melting point or 1HNMR spectra with ones reported in the literature [29a-29e].
92%	With 1,1'-(ethane-1,2-diyl)dipyridinium bistribromide at 20℃; for 0.5h;
91%	With bromine In dichloromethane
91%	With 1,3-di-n-butyl-1H-imidazol-3-ium tribromide at 20℃; for 0.25h; Neat (no solvent); regioselective reaction;
91%	With bromine In dichloromethane at 20℃; for 0.5h;	1 Example 1: Preparation of Compound IV from 4-methoxyphenol 4-methoxyphenol (1.24 g, 10 mmol)Soluble in a solution of CH2Cl2 (60ml),Slowly drip in Br2 (0.51ml) at room temperature, 10.1mmol),Stirring was continued for 30 min and filtered to give compound IV (1.84 g, 91%).
90%	With tetra-N-butylammonium tribromide In methanol; dichloromethane for 0.5h; Ambient temperature; reagent 1.0 equivalent;
90%	With hexamethonium bis(tribromide) In neat (no solvent) for 0.333333h; Green chemistry; regioselective reaction;
90%	With bromine In dichloromethane at 0 - 20℃; for 1.5h; Inert atmosphere; Schlenk technique;
88%	With bromine In dichloromethane at 20℃; for 20h; Inert atmosphere;
86%	With N-Bromosuccinimide In acetonitrile for 1h; Ambient temperature;
86%	With bromine In dichloromethane at -5℃; for 1h;
84%	With ethyl triphenylphosphonium tribromide In acetonitrile at 20℃; for 0.25h;
84%	With trimethylsilyl bromide; 4,4’-dichlorodiphenyl sulfoxide In acetonitrile at 25℃; for 6h; Inert atmosphere; regioselective reaction;
82%	With glacial acetic acid; potassium bromide In water monomer; glacial acetic acid at 35℃; regioselective reaction;	4.2. General Procedure for the Bromination General procedure: 0.11 g (1.0 mmol) of 4-methylphenol, 5 mL of acetic acid, 0.5 mL of water, and 0.12 g (1.0 mmol)potassium bromide were placed in round-bottomed flask. Then, 0.19 g (0.2 mmol)ZnAl-BrO3--LDHs was added in the flask under stirring at 35 °C. After the addition, stirring wascontinued to the end of reaction (monitored by thin layer chromatography). The residualZnAl-BrO3--LDHs were removed by centrifugation. The product was extracted with 3 × 10 mLdichloromethane. The combined extract was washed with sodium sulfite solution, brine, and dried(Na2SO4). Evaporation of the solvent left the crude product. The crude product was purified bycolumn chromatography over silica gel (ethyl acetate-petroleum ether) to obtain pure product.
81%	With tetra-N-butylammonium tribromide In methanol; dichloromethane at 20℃;
81%	With trimethylsilyl bromide; 4,4’-dichlorodiphenyl sulfoxide In acetonitrile at 25℃; for 6h; Inert atmosphere;	10 Example 10 Preparation of 2-bromo-4-methoxyphenol by 4-methoxyphenol and trimethylbromosilane Phenol is added sequentially to the tubular reactor(62.0 mg, 0.50 mmol), Trimethylbromosilane (84.2 mg, 0.55 mmol, 1.1 equiv.), Di-(4-chlorophenyl) sulfoxide (148.5 mg, 0.55 mol) and acetonitrile (1.0 mL), It was then evacuated, protected with nitrogen and reacted at 25 ° C for 6 h. After the reaction was completed by GC-MS, filtered, and the filter cake was washed with a small portion of cold acetonitrile, and the recovered cake was bis-(4-chlorophenyl) sulfide (102.8 mg).1M sodium hydroxide (0.6 mL) was added to the filtrate, then transferred to a sep. funnel and extracted with ethyl acetate 5 mL3. After spinning, it is combined with the above-mentioned filter cake bis-(4-chlorophenyl) sulfide.a mixture of bis-(4-chlorophenyl) sulfoxide (remaining reaction) and bis-(4-chlorophenyl) sulfide (reacted by reaction), The mixture is then completely converted to bis-(4-chlorophenyl) sulfoxide via oxidation. It can be used as a bromination reaction of the next phenol compound as an activator (total recovery is 90%). The obtained aqueous phase was extracted, and 1 M diluted hydrochloric acid was added to adjust the pH to 1, Then add ethyl acetate 5 mL3 again to extract and combine the organic phases. Dry over anhydrous sodium sulfate, spin dry to produce 2-bromo 4-methoxyphenol, The isolated yield was 81% (product purity 95%) (selectivity 95/5).
80%	With bromine In methanol at 0 - 20℃;
79%		R.8.1 Reference Example 8 (1) 4-Methoxyphenol (124.14 g) was treated in the same manner as described in Reference example 4 (1) to give 161 g of 2-bromo-4-methoxyphenol (yield: 79%, melting point: 37°-38° C.).
75%	With N-Bromosuccinimide In acetonitrile at 20℃;
74%	With bromine In chloroform at 0 - 20℃;
73%	With bromine In methanol at 0 - 20℃;
73%	With bromine In dichloromethane at -5 - 20℃; for 1h; Inert atmosphere;
73%	With hydrogen bromide; dimethyl sulfoxide In water monomer; ethyl acetate at 60℃; for 4h;
68%	With copper (II) bromide In acetonitrile at 20℃; for 12h;
57%	With bromine In carbon disulfide at 0℃; for 0.5h;	VII A solution of 2.6 mL (100 mMol) bromine in 10 mL carbon disulfide was added dropwise over 30 minutes to a solution of 12.4 gm (100 mMol) 4-methoxyphenol in 20 mL carbon disulfide at 0° C. After 30 minutes an additional 1 mL of bromine in 10 mL carbon disulfide are added dropwise. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in diethyl ether. This solution was washed sequentially with 100 mL water and 100 mL saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with a gradient of hexane containing from 0 to 20% ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide 11.6 gm (57%) of the desired compound as a crystalline solid.1H-NMR(CDCl3): δ 7.0 (d, 1H), 6.95 (d, 1H), 6.8 (dd, 1H), 5.15 (s, 1H), 3.75 (s, 3H).
57%	With bromine In carbon disulfide at 0℃; for 1h;	VII A solution of 2.6 mL (100 mMol) bromine in 10 mL carbon disulfide was added dropwise over 30 minutes to a solution of 12.4 gm (100 mMol) 4-methoxyphenol in 20 mL carbon disulfide at 0°C. After 30 minutes an additional 1 mL of bromine in 10 mL carbon disulfide are added dropwise. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in diethyl ether. This solution was washed sequentially with 100 mL water and 100 mL saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with a gradient of hexane containing from 0 to 20% ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide 11.6 gm (57%) of the desired compound as a crystalline solid.1H-NMR(CDCl3): δ 7.0 (d, 1H), 6.95 (d, 1H), 6.8 (dd, 1H). 5.15 (s, 1H), 3.75 (s, 3H).
46%	With [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-κN1,κN1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC]iridium hexafluorophosphate; dimethyl α-bromomalonate In acetonitrile at 20℃; for 21h; Inert atmosphere; Schlenk technique; Irradiation;
25%	With N-Bromosuccinimide In acetonitrile at 20℃; for 2h;
	With chloroform; bromine
	With carbon disulfide; bromine
	With bis(dimethylacetamide)hydrogen tribromide In chloroform Ambient temperature; Yield given;
	With tetrabutylammonium bromide In methanol; dichloromethane Yield given;
	With N-Bromosuccinimide
	With bromine In N,N-dimethyl-formamide	1.a a a 2-Bromo-4-methoxyphenol To a solution of 4-methoxyphenol (13.00 g, 104.84 mmol) in DMF (50 mL) was added bromine (5.40 mL, 104.84 mmol) at 0° C. The reaction was allowed to warm to room temperature. After stirring for 2 h the reaction was quenched with water and extracted with ethyl acetate (3*200 mL). The combined organic extracts were washed with brine and dried (Na2 SO4). Removal of the solvent under reduced pressure gave 21.28 g of the crude title compound as a dark oil: 1 H NMR (250 MHz, CDCl3) d 7.49 (b, 1H), 6.96 (d, 1H), 6.72-6.62 (m, 2H), 3.71 (s, 3H).
	With bromine In dichloromethane at -78 - 20℃; Inert atmosphere;	4-Methoxyphenol (5.0 g, 40.2 mmol, 1.0 eq.) in DCM (200 ml) was cooled to -78 0C in an inert atmosphere and bromine (2.5 ml, 48.3 mmol, 1.2 eq.) was added dropwise to the reaction mixture. After complete addition, the mixture was warmed to ambient temperature and stirred for 2 h. The reaction was quenched by adding 50 ml of saturated Na2S2O3 and extracted with DCM (100 ml X 2). The combined organic layer was washed with water (100 ml) and brine (100 ml), dried over sodium sulfate, and concentrated under reduced pressure to afford 2-bromo-4-methoxyphenol.
	With bromine In chloroform at 0 - 20℃; for 2h;	2.A Step A: 2-bromo-4-methoxyphenol To a solution of 4-methoxyphenol (10 g, 81 mmol) in CHCl3 (50 mL) was added BR2 (4 mL, 78 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h, then allowed to warm to room temperature, the mixture was stirred at room temperature for 1 h. The resulting mixture was diluted with dichloromethane (500 mL) and washed with saturated NaHSO3 (3*100 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (16.6 g, 100%) as an off-white solid which was used in the next step.
	With bromine In chloroform at 0 - 20℃; for 2h;	2.A Example 2: Synthesis of compounds 2.1-2.37 Step A: 2-bromo-4-methoxyphenol Example 2: Synthesis of compounds 2.1-2.37 Step A: 2-bromo-4-methoxyphenol A solution of 4-methoxyphenol (10g, 81mmol) in CHCl3 (50mL) was added Br2 (4mL, 78mmol) at 0°C. The mixture was stirred at 0°C for 1 hour. The mixture was then warmed to room temperature and stirred at room temperature for 1 hour. The resulting mixture was diluted in methylene chloride (a 500 mL), treated with saturated NaHSO3 (3 × 100mL), washed with saturated brine (200mL), dried over anhydrous sodium sulfate, filtered and concentrated to give the target compound as an off-white solid (16.6g, 100%). This compound was used directly without further purification in the next reaction.
129 mg	With N-Bromosuccinimide In acetonitrile at 0 - 20℃; for 10h; Inert atmosphere;
11.6 gm (57%)	With bromine In carbon disulfide; diethyl ether; ethyl acetate	VII 2-bromo-4-methoxyphenol 2-bromo-4-methoxyphenol A solution of 2.6 mL (100 mMol) bromine in 10 mL carbon disulfide was added dropwise over 30 minutes to a solution of 12.4 gm (100 mMol) 4-methoxyphenol in 20 mL carbon disulfide at 0°C. After 30 minutes an additional 1 mL of bromine in 10 mL carbon disulfide are added dropwise. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in diethyl ether. This solution was washed sequentially with 100 mL water and 100 mL saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluding with a gradient of hexane containing from 0 to 20% ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide 11.6 gm (57%) of the desired compound as a crystalline solid. 1H-NMR(CDCl3): δ 7.0 (d, 1H), 6.95 (d, 1H), 6.8 (dd, 1H), 5.15 (s, 1H), 3.75 (s, 3H).
	With bromine; glacial acetic acid at 0℃; for 0.5h;	2. General Procedure for Aryne Precursors 1a-1m The synthesis of compound 1a was examplified. A solution of phenol (1.00 g, 10.63 mmol) and Br2 (0.49 mL, 9.56 mmol) in AcOH (7 mL) was stirred for 30 min at 0 °C, the reaction mixture was poured into a separatory funnel with ice water (10 mL) and the aqueous phase was extracted with DCM (3 × 15 mL). The combined organic extracts were washed with saturated NaCl (aq) and dried over MgSO4 and concentrated under reduced pressure. The crude product was dissolved in THF (15 mL) and added to HMDS (2.44 mL, 11.69 mmol) for reflux at 70 °C for 2 h. The solvent was evaporated under reduced pressure and the crude product was dissolved in THF (15 mL). Finally, the solution was cooled to -78 °C and n-BuLi (5.53 mL, 2.5 M, 13.82 mmol) was added dropwise and stirred for 1 h. Tf2O (1.97 mL, 11.69 mmol) was added dropwise and was stirred for 1.5 h. Cold saturated aqueous NaHCO3 (20 mL) was added after separation, and the aqueous layer was extracted with Et2O. The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to give 1a. The remaining compounds 1b-1m (structures showed in Figure 1) were obtained by the same synthetic route.
	With [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-κN1,κN1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC]iridium hexafluorophosphate; dimethyl α-bromomalonate In acetonitrile for 16h; Glovebox; Inert atmosphere; Irradiation;	General procedure: To each reaction vessel was added the catalyst stock solution (100 μL, 0.0015 mmol,5.0 mol%), one quencher stock solution (200 μL, 0.03 mmol, 1.0 equiv) and one radicalacceptor solution (200 μL, 0.06 mmol, 2.0 equiv). The reaction matrix covering all possiblepair-wise quencher-acceptor combinations is shown in Figure S8. After sealing all reactionvessels with a polythene sheet, the well plate was equipped with an appropriate 8 x 12 LEDirradiation system. The whole setup was placed over a magnetic stir plate and irradiated for16 h.
	With bromine In DMF (N,N-dimethyl-formamide) at 20℃; for 2h;	I.a a) 2-Bromo-4-methoxyphenol To a solution of 4-methoxyphenol (13.00 g, 104.84 mmol) in DMF (50 mL) was added bromine (5.40 mL, 104.84 mmol) at 0° C. The reaction was allowed to warm to room temperature. After stirring for 2 h the reaction was quenched with water and extracted with ethyl acetate (3×200 mL). The combined organic extracts were washed with brine and dried (Na2SO4). Removal of the solvent under reduced pressure gave 21.28 g of the crude title compound as a dark oil: 1H NMR (250 MHz. CDCl3) d 7.49 (b, 1H), 6.96 (d, 1H), 6.72-6.62 (m, 2H), 3.71 (s, 3H).
	With bromine; potassium hydroxide In dichloromethane at 0℃; for 0.833333h; Inert atmosphere; Schlenk technique; Sealed tube;
	With bromine In dichloromethane at 0℃; for 0.833333h; Inert atmosphere; Schlenk technique; Sealed tube;

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[41]Bhatt, Suchitra; Nayak, Sandip K. [Synthetic Communications, 2007, vol. 37, # 8, p. 1381 - 1388]
[42]Current Patent Assignee: ELI LILLY & CO - US7045545, 2006, B1 Location in patent: Page/Page column 21
[43]Current Patent Assignee: ELI LILLY & CO - EP1204659, 2003, B1 Location in patent: Page/Page column 16
[44]Hopkinson, Matthew N.; Gómez-Suárez, Adrián; Teders, Michael; Sahoo, Basudev; Glorius, Frank [Angewandte Chemie - International Edition, 2016, vol. 55, # 13, p. 4361 - 4366][Angew. Chem., 2016, vol. 128, # 13, p. 4434 - 4439,6]
[45]Wienhold, Max; Molloy, John J.; Daniliuc, Constantin G.; Gilmour, Ryan [Angewandte Chemie - International Edition, 2021, vol. 60, # 2, p. 685 - 689][Angew. Chem., 2021, vol. 133, # 2, p. 695 - 699,5]
[46]Nametkin et al. [Doklady Akademii Nauk SSSR, 1951, vol. 77, p. 293,295][Chem.Abstr., 1951, p. 10231]
[47]Irvine; Smith [Journal of the Chemical Society, 1927, p. 74]
[48]Mikhailov, V. A.; Savelova, V. A.; Rodygin, M. Yu. [Russian Journal of Organic Chemistry, 1993, vol. 29, # 11.2, p. 1868 - 1870][Zhurnal Organicheskoi Khimii, 1993, vol. 29, # 11, p. 2251 - 2254]
[49]Curran, Dennis P.; Xu, Jinyou [Journal of the American Chemical Society, 1996, vol. 118, # 13, p. 3142 - 3147]
[50]Lautens, Mark; Fang, Yuan-Qing [Organic Letters, 2003, vol. 5, # 20, p. 3679 - 3682]
[51]Current Patent Assignee: GLAXOSMITHKLINE PLC - US5958968, 1999, A
[52]Current Patent Assignee: ABBVIE INC - WO2010/127208, 2010, A1 Location in patent: Page/Page column 60
[53]Current Patent Assignee: BEIGENE LTD. - US2015/45355, 2015, A1 Location in patent: Paragraph 0378-0380
[54]Current Patent Assignee: BEIGENE LTD. - CN105348299, 2016, A Location in patent: Paragraph 0358; 0565; 0566; 0567; 0568; 0569
[55]Camargo Solórzano, Patricia; Brigante, Federico; Pierini, Adriana B.; Jimenez, Liliana B. [Journal of Organic Chemistry, 2018, vol. 83, # 15, p. 7867 - 7877]
[56]Current Patent Assignee: ELI LILLY & CO - EP1204654, 2002, A1
[57]Lei, Meng; Miao, Hang; Wang, Xueyuan; Zhang, Wen; Zhu, Chengjian; Lu, Xiaqiang; Shen, Jian; Qin, Yanru; Zhang, Haoyang; Sha, Sijia; Zhu, Yongqiang [Tetrahedron Letters, 2019, vol. 60, # 20, p. 1389 - 1392]
[58]Strieth-Kalthoff; Henkel, Christian; Teders, Michael; Kahnt, Axel; Knolle, Wolfgang; Gómez-Suárez, Adrián; Dirian, Konstantin; Alex, Wiebke; Bergander; Daniliuc, Constantin G.; Abel; Guldi, Dirk M.; Glorius [Chem, 2019, vol. 5, # 8, p. 2183 - 2194]
[59]Current Patent Assignee: GLAXOSMITHKLINE PLC - US6353116, 2002, B1 Location in patent: Page column 20
[60]Grünenfelder, Denise C.; Navarro, Raul; Wang, Haoxuan; Fastuca, Nicholas J.; Butler, John R.; Reisman, Sarah E. [Angewandte Chemie - International Edition, 2022, vol. 61, # 16][Angew. Chem., 2022, vol. 134, # 16]
[61]Grünenfelder, Denise C.; Navarro, Raul; Wang, Haoxuan; Fastuca, Nicholas J.; Butler, John R.; Reisman, Sarah E. [Angewandte Chemie - International Edition, 2022, vol. 61, # 16][Angew. Chem., 2022, vol. 134, # 16]

2
[ 17332-11-5 ]
[ 107-30-2 ]
[ 195314-47-7 ]

Reference： [1]Heterocycles,2015,vol. 90,p. 1387 - 1395
[2]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1961 - 1965
[3]Tetrahedron,2004,vol. 60,p. 9675 - 9686

3
[ 17332-11-5 ]
[ 59376-64-6 ]
2-bromo-4-methoxyphenyl (E)-3-trimethylsilyl-2-propenyl ether [ No CAS ]

Reference： [1]Organic Letters,2002,vol. 4,p. 2225 - 2228

4
[ 4175-78-4 ]
[ 17332-11-5 ]
[ 936247-39-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1961 - 1965

5
[ 17332-11-5 ]
[ 5307-05-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1961 - 1965

6
[ 17332-11-5 ]
[ 67247-13-6 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 1581 - 1587

7
[ 17332-11-5 ]
[ 90484-47-2 ]
[ 128868-60-0 ]

Yield	Reaction Conditions	Operation in experiment
		VII 2-bromo-4-methoxyphenol Beginning with 11.5 gm (56.9 mMol) 2-bromo-4-methoxyphenol, 4.5 gm (35%) of the title compound were prepared essentially by the procedure described in Preparation IV. EA: Calculated for C9H7BrO2: Theory: C, 47.61; H, 3.11. Found: C, 47.79; H, 3.13.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - EP1204654, 2002, A1

8
[ 17332-11-5 ]
[ 132559-91-2 ]
[ 1259312-63-4 ]

Reference： [1]Dalton Transactions,2010,vol. 39,p. 10391 - 10400

9
[ 17332-11-5 ]
[ 132559-91-2 ]
[ 1259312-64-5 ]

Reference： [1]Dalton Transactions,2010,vol. 39,p. 10391 - 10400

10
[ 17332-11-5 ]
[ 14900-39-1 ]
[ 1275593-42-4 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 1881 - 1883

11
[ 17332-11-5 ]
[ 14900-39-1 ]
[ 62594-98-3 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 1881 - 1883

12
[ 13057-17-5 ]
[ 17332-11-5 ]
[ 195314-47-7 ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2013,vol. 56,p. 321 - 324
[2]Advanced Synthesis and Catalysis,2018,vol. 360,p. 4005 - 4011
[3]European Journal of Organic Chemistry,2019,vol. 2019,p. 7836 - 7841

13
[ 64584-92-5 ]
[ 17332-11-5 ]
(S)-2-bromo-4-methoxy-1-(pent-4-en-2-yloxy)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 3h;	(S)-2-Bromo-4-methoxy-1- (pent-4-en-2 -yloxy) benzene: (S)-2-Bromo-4-methoxy-1- (pent-4-en-2 -yloxy) benzene: A mixture of 2- bromo-4-methoxyphenol (300 mg, 1.478 mmol), (R)-pent-4-en-2-ol (255 mg, 2.96 mmol), triphenylphosphine (775 mg, 2.96 mmol) and DEAD (515 mg, 2.96 mmol) in THF (20 mL) was stirred at rt for 3 h. It was then concentrated and purified bybiotage, eluting with 10% EtOAc/hexane to isolate (S)-2-bromo-4-methoxy-1-(pent-4-en-2-yloxy)benzene (300 mg, 75%) as a colorless oil. ‘H NMR (400MHz, CDC13)ö 7.12 (d, J=2.9 Hz, 1H), 6.93 - 6.87 (m, 1H), 6.84 - 6.78 (m, 1H), 5.92 (ddt, J=17.2,10.2, 7.1 Hz, 1H), 5.21 - 5.09 (m, 2H), 4.32 (sxt, J=6.1 Hz, 1H), 3.78 (s, 3H), 2.62 -2.48 (m, 1H), 2.46 - 2.35 (m, 1H), 1.33 (d, J6.1 Hz, 3H).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2015/126376, 2015, A1 Location in patent: Page/Page column 57

14
[ 17332-11-5 ]
[ 3107-19-5 ]
2-(2-bromo-4-methoxyphenoxy)-1,3-dichloro-5-nitrobenzene [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 4790 - 4799

15
[ 17332-11-5 ]
[ 41317-15-1 ]
C₂₁H₂₀BrNO₃ [ No CAS ]

Reference： [1]ACS Catalysis,2017,vol. 7,p. 2446 - 2451

16
[ 17332-11-5 ]
[ 1413732-47-4 ]
2,2-difluoro-5-methoxybenzo[d][1,3]oxathiole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium fluoride; In acetonitrile; at 100.0℃; for 16.0h;Industrial scale;	Place a teflon magnet in a 25 mL reaction tube and add 0.30 mmol of 2-bromo-6-methoxy-phenol, 0.36 mmol of copper (bpy) CuSCF3, 0.339 mmol of potassium fluoride and 2.5 mL acetonitrile, stirred at 100 in a closed system for 16 h, extracted three times with n-pentane,The organic phases were combined, washed with water and then evaporated to remove the organic solvent. The obtained crude product was purified by silica gel column chromatography using n-pentane and diethyl ether (10: 1, v / v)2,2-Difluoro-6-methoxy-1.3-benzoxathiane (99% yield).

Reference： [1]Patent: CN107382956,2017,A .Location in patent: Paragraph 0022
[2]Organic Letters,2018,vol. 20,p. 481 - 484

17
[ 17332-11-5 ]
[ 40492-52-2 ]

Reference： [1]Patent: WO2017/218960,2017,A1

18
[ 17332-11-5 ]
[ 115929-59-4 ]

Yield	Reaction Conditions	Operation in experiment
	With nitric acid; In ethyl acetate; at 0 - 20℃; for 10.0h;	2.5 g of 2-bromo-4-methoxyphenol was dissolved in ethyl acetate (125 mL), and then 70% nitric acid (0.8 mL, 1.0 equivalent) was added thereto at 0 C. over 10 minutes, followed by stirring at room temperature for 10 hours. The formation of the product was confirmed by TLC, and then solid sodium hydrogen carbonate was added to adjust the pH to 7. The reaction mixture was filtered and the filtrate was extracted using ethyl acetate. Thereafter, the organic phase was dried over anhydrous magnesium sulfate, followed by filtration, and thus obtaining as a crude product 2.8 g of the title compound obtained by vacuum concentration of the filtrate.MS (ESI) m/z: 248 (M+H)+

Reference： [1]Patent: US2019/322686,2019,A1 .Location in patent: Paragraph 1140; 1141
[2]Patent: EP3815687,2021,A1 .Location in patent: Paragraph 0130

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	17332-11-5	MDL No. :	MFCD02113712
Formula :	C₇H₇BrO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	203.03	Pubchem ID :	-
Synonyms :

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	42.66
TPSA :	29.46 Å²

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) :	-5.76 cm/s

Log Po/w (iLOGP) :	2.16
Log Po/w (XLOGP3) :	2.5
Log Po/w (WLOGP) :	2.16
Log Po/w (MLOGP) :	1.91
Log Po/w (SILICOS-IT) :	2.02
Consensus Log Po/w :	2.15

[ CAS No. 17332-11-5 ] {[proInfo.proName]}

Quality Control of [ 17332-11-5 ]

Related Doc. of [ 17332-11-5 ]

Product Details of [ 17332-11-5 ]

Calculated chemistry of [ 17332-11-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 17332-11-5 ]

Application In Synthesis of [ 17332-11-5 ]

[ 17332-11-5 ] Synthesis Path-Upstream 1~13

[ 17332-11-5 ] Synthesis Path-Downstream 1~18

Related Functional Groups of
[ 17332-11-5 ]

Aryls

Bromides

Ethers

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

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Inquiry

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

Log S (ESOL) :	-3.05
Solubility :	0.18 mg/ml ; 0.000888 mol/l
Class :	Soluble
Log S (Ali) :	-2.76
Solubility :	0.35 mg/ml ; 0.00172 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.81
Solubility :	0.316 mg/ml ; 0.00156 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.5

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

Yield	Reaction Conditions	Operation in experiment
100%	With bromine In chloroform at 0 - 20℃; for 2 h;	To a solution of 4-methoxyphenol (10 g, 81 mmol) in CHC13 (50 mL) was added BR (4 mL, 78 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 h, then allowed to warm to room temperature, the mixture was stirred at room temperature for 1 h. The resulting mixture was diluted with dichloromethane (500 mL) and washed with saturated NaHS03 (3x 100 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (16.6 g, 100percent) as an off- white solid which was used in the next step.
100%	With bromine In chloroform at 0 - 20℃; for 2 h;	To a solution of 4-methoxyphenol (10 g, 81 mmol) in CHC1₃ (50 mL) was added Br₂(4 mL, 78 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 h, then allowed to warm to room temperature, the mixture was stirred at room temperature for 1 h. The resulting mixture was diluted with dichloromethane (500 mL) and washed with saturated NaHS0₃ (3 ^χ 100 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (16.6 g, 100percent) as an off- white solid which was used in the next step.
100%	With bromine In chloroform at 0 - 20℃; for 2 h;	To a solution of 4-methoxyphenol (10 g, 81 mmol) in CHCl3 (50 mL) was added BR²(4 mL, 78 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h, then allowed to warm to room temperature, the mixture was stirred at room temperature for 1 h. The resulting mixture was diluted with dichloromethane (500 mL) and washed with saturated NaHSO3 (3×100 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (16.6 g, 100percent) as an off-white solid which was used in the next step.

100%	With bromine In dichloromethane at 40℃; for 1 h; Cooling with ice	To a solution of Example 2a (51.2 g, 0.41 mol) in DCM (0.5 L) cooled in an ice bath was added Br₂ (66 g, 0.41 mol) dropwise. After addition, the resulting solution was stirred at 40 °C for 1 h. The reaction mixture was washed with water (400 mL*3), NaHC0₃ (200 mL) and brine, dried over Na₂S0₄ and concentrated to give the desired product (Example 2b, 86.1 g, yield 100percent) as colorless oil, which was used in the next step without further purification.
98.7%	With bromine In dichloromethane for 2 h; Cooling with ice	Br2 (64.7 g, 403 mmol) dissolved in CH2Cl2 (30 mL) was slowly addeddropwise to a solution of p-methoxyphenol (2) (50 g, 403 mmol) in CH2Cl2 (200 mL) under the ice bath.The reaction mixture was stirred for 2 h then poured into ice water and extracted with CH2Cl2. Theorganic layer was washed with a solution of saturated aqueous NaHCO3 and NaCl in sequence and thendried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure and the residue wassubjected to flash column chromatography (petroleum ether: EtOAc, 20:1, V/V) to give 3 (80.0 g, 98.7percent)as colourless solid
93%	With o-xylylene bis(triethylammonium tribromide) In acetonitrile at 20℃; for 0.0833333 h;	General procedure: To a magnetic solution of aromatic compound (1 mmol)in acetonitrile (5 mL), OXBTEATB (0.233 g, 0.5 mmol) wasadded and stirred at room temperature for the appropriatetime (Table 1). The reaction was monitored by TLC (eluent:n-hexane/ethyl acetate: 5/1). The reaction mixture was transferredinto a separatory funnel after filtration of OXBTEABand was extracted with water (15 mL) and dichloromethane(20 mL). The organic layer was dried over anhydrousNa2SO4, and the solvent was concentrated in a rotary evaporator.The crude product was purified by passing it over acolumn of silica gel using a mixture of n-hexane and ethylacetate as the eluent. In order to regenerate the reagent, whitesolid was treated with liquid bromine. All the product structureswere confirmed by comparison of melting point or 1HNMR spectra with ones reported in the literature [29a-29e].
57%	With bromine In carbon disulfide at 0℃; for 0.5 h;	A solution of 2.6 mL (100 mMol) bromine in 10 mL carbon disulfide was added dropwise over 30 minutes to a solution of 12.4 gm (100 mMol) 4-methoxyphenol in 20 mL carbon disulfide at 0° C. After 30 minutes an additional 1 mL of bromine in 10 mL carbon disulfide are added dropwise. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in diethyl ether. This solution was washed sequentially with 100 mL water and 100 mL saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with a gradient of hexane containing from 0 to 20percent ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide 11.6 gm (57percent) of the desired compound as a crystalline solid.¹H-NMR(CDCl₃): δ 7.0 (d, 1H), 6.95 (d, 1H), 6.8 (dd, 1H), 5.15 (s, 1H), 3.75 (s, 3H).
57%	With bromine In carbon disulfide at 0℃; for 1 h;	A solution of 2.6 mL (100 mMol) bromine in 10 mL carbon disulfide was added dropwise over 30 minutes to a solution of 12.4 gm (100 mMol) 4-methoxyphenol in 20 mL carbon disulfide at 0°C. After 30 minutes an additional 1 mL of bromine in 10 mL carbon disulfide are added dropwise. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in diethyl ether. This solution was washed sequentially with 100 mL water and 100 mL saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with a gradient of hexane containing from 0 to 20percent ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide 11.6 gm (57percent) of the desired compound as a crystalline solid.1H-NMR(CDCl3): δ 7.0 (d, 1H), 6.95 (d, 1H), 6.8 (dd, 1H). 5.15 (s, 1H), 3.75 (s, 3H).
57%	With bromine In carbon disulfide; diethyl ether; ethyl acetate	2-bromo-4-methoxyphenol A solution of 2.6 mL (100 mMol) bromine in 10 mL carbon disulfide was added dropwise over 30 minutes to a solution of 12.4 gm (100 mMol) 4-methoxyphenol in 20 mL carbon disulfide at 0°C. After 30 minutes an additional 1 mL of bromine in 10 mL carbon disulfide are added dropwise. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in diethyl ether. This solution was washed sequentially with 100 mL water and 100 mL saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluding with a gradient of hexane containing from 0 to 20percent ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide 11.6 gm (57percent) of the desired compound as a crystalline solid. ¹H-NMR(CDCl₃): δ 7.0 (d, 1H), 6.95 (d, 1H), 6.8 (dd, 1H), 5.15 (s, 1H), 3.75 (s, 3H).
57%	With bromine In carbon disulfide; diethyl ether; ethyl acetate	2-bromo-4-methoxyphenol A solution of 2.6 mL (100 mMol) bromine in 10 mL carbon disulfide was added dropwise over 30 minutes to a solution of 12.4 gm (100 mMol) 4-methoxyphenol in 20 mL carbon disulfide at 0°C. After 30 minutes an additional 1 mL of bromine in 10 mL carbon disulfide are added dropwise. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in diethyl ether. This solution was washed sequentially with 100 mL water and 100 mL saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluding with a gradient of hexane containing from 0 to 20percent ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide 11.6 gm (57percent) of the desired compound as a crystalline solid. ¹H-NMR(CDCl₃): δ 7.0 (d, 1H), 6.95 (d, 1H), 6.8 (dd, 1H), 5.15 (s, 1H), 3.75 (s, 3H).

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
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P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
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P270	Do not eat, drink or smoke when using this product.
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P272	Contaminated work clothing should not be allowed out of the workplace.
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P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
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P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
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P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
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P370	In case of fire:
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P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
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