116632-23-6|3-Bromo-5-nitrophenol| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 116632-23-6 ] Purity: 95% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 116632-23-6 ]

CAS No. :	116632-23-6
Formula :	C₆H₄BrNO₃
M.W :	218.01
SMILES Code :	OC1=CC(Br)=CC(=C1)[N+]([O-])=O
MDL No. :	MFCD09965960
InChI Key :	VJQGLUHOAIZTNK-UHFFFAOYSA-N
Pubchem ID :	10488984

Safety of [ 116632-23-6 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H302-H315-H317-H318-H410
Precautionary Statements:	P261-P264-P270-P272-P273-P280-P301+P312+P330-P302+P352-P305+P351+P338+P310-P333+P313-P391-P501
Class:	9
UN#:	3077
Packing Group:	Ⅲ

Computational Chemistry of [ 116632-23-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	44.99
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	66.05 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.09
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.22
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.06
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.05
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-0.1
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.47

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.56
Solubility	0.0603 mg/ml ; 0.000277 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-4.28
Solubility	0.0115 mg/ml ; 0.0000525 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.06
Solubility	1.89 mg/ml ; 0.00867 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	Yes
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.34 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	2.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.22

Application In Synthesis of [ 116632-23-6 ]

* 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 [ 116632-23-6 ]

[ 116632-23-6 ] Synthesis Path-Downstream 1~35

1
[ 618-64-4 ]
[ 116632-23-6 ]

References: [1]Chemische Berichte,1909,vol. 42,p. 2192.

2
[ 16618-67-0 ]
[ 116632-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	With boron tribromide; In hexane; dichloromethane; ethyl acetate;	Step C 3-Bromo-5-nitrophenol A solution of 3-bromo-5-nitroanisole, as described above in Step B, (2.4 g, 10.3 mmol) in methylene chloride (50 mL) was cooled to 0° C. and treated with boron tribromide (1M in CH2Cl2, 158 mL, 158 mmol), giving a clear purple solution. The reaction was warmed slowly to room temperature and stirred at room temperature overnight and heated at reflux for 2.5 hours. The reaction was poured into ice/water, the layers were separated and extracted with methylene chloride. The aqueous layer was neutralized with aqueous saturated NaHCO3 and extracted with ethyl acetate. The organic layers were combined, dried (MgSO4), filtered and concentrated in vacuo. This material was purified by column chromatography (10:1 to 5:1 hexane:ethyl acetate). The fractions containing the product contaminated with the bromoanisole were pooled, concentrated and purified using radial, thin layer chromatography (hexane to 5:1 hexane:ethyl acetate) to give 3-bromo-5-nitrophenol as a yellow solid. 1H NMR (delta, MeOH-d4): 7.81 (1H, m), 7.57 (1H, m), 7.32 (1H, m).
		Example 34; BBr3 (8.62 mL of a 1.0 M solution in CH2Cl2; 8.62 mmol) was added to a solution of 1-bromo-3-methoxy-5-nitrobenzene (500 mg, 2.16 mmol) in CH2Cl2 (5 mL) at -20° C. The reaction was allowed to warm to RT and stirred at RT overnight, then was cautiously quenched with MeOH (30 mL) and stirred for 1 h at RT. Volatiles were removed in vacuo to give crude Part A Compound as a brown solid. 1H NMR (500 MHz, CDCl3) delta ppm 7.94 (s, 1 H), 7.62-7.64 (m, 1 H), 7.33 (s, 1 H), 5.84 (s, 1 H); LCMS Method A (ESI, positive ion spectrum): (M+H)/z=220, tR=3.14 min.
		To a 0.70 M solution of l-bromo-3-methoxy-5-nitrobenzene (1.0 eq) in DCM was added a 1.0 M solution of boron tribromide in DCM (2.2 eq) while cooling in an ice/water bath. The reaction was stirred for 4 d at ambient temperature. The mixture was cooled to -78 C and quenched with methanol (15 eq). The mixture was returned to ambient temperature. Volatiles were removed under reduced pressure. The crude material was triturated with 5 : 1 watepimethanol (210 mL), filtered, and rinsed with additional solvent to give 31.9 g of the desired product as a lavender-grey solid after drying in a desiccator.

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1908,vol. 27,p. 36.
[2]Recueil des Travaux Chimiques des Pays-Bas,1968,vol. 87,p. 1327 - 1338.
[3]Patent: US6458935,2002,B1 .
[4]Patent: US2009/30046,2009,A1 .Location in patent: Page/Page column 33-34.
[5]Patent: WO2009/153313,2009,A1 .Location in patent: Page/Page column 181.

3
[ 116632-23-6 ]
2,3,4,6-tetrabromo-5-nitro-phenol [ No CAS ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1908,vol. 27,p. 36.

4
[ 116632-23-6 ]
benzoic acid-(3-bromo-5-nitro-phenyl ester) [ No CAS ]

References: [1]Chemische Berichte,1909,vol. 42,p. 2192.

5
[ 116632-23-6 ]
Dichlorphosphorsaeure-5-brom-3-nitro-phenylester [ No CAS ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1968,vol. 87,p. 1327 - 1338.

6
GENERIC INORGANIC CATION; 3-bromo-5-nitro-phenolate [ No CAS ]
[ 116632-23-6 ]

References: [1]Synthetic Communications,1997,vol. 27,p. 2793 - 2797.

7
[ 618-64-4 ]
[ 10035-10-6 ]
sodium nitrite [ No CAS ]
[ 116632-23-6 ]

References: [1]Chemische Berichte,1909,vol. 42,p. 2192.

8
5-bromo-3-nitro-anisyl [ No CAS ]
[ 116632-23-6 ]

References: [1]Journal of the Chemical Society,1926,p. 2078.

9
[ 401-99-0 ]
[ 116632-23-6 ]
3'-bromo-3,5'-dinitro-5-trifluoromethyldiphenyl ether [ No CAS ]

References: [1]Russian Journal of Organic Chemistry,2002,vol. 38,p. 47 - 58.
[2]Journal of Physical Organic Chemistry,2000,vol. 13,p. 630 - 633.

10
[ 454-73-9 ]
[ 116632-23-6 ]
3'-bromo-3,5'-dinitro-5-trifluoromethyldiphenyl ether [ No CAS ]

References: [1]Russian Journal of Organic Chemistry,2002,vol. 38,p. 47 - 58.
[2]Journal of Physical Organic Chemistry,2000,vol. 13,p. 630 - 633.

11
2-(3-bromo-5-nitro-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane [ No CAS ]
[ 116632-23-6 ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 4897 - 4901.

12
[ 116632-23-6 ]
[ 98-88-4 ]
[ 99769-19-4 ]
3'-benzoylamino-5'-hydroxy-biphenyl-3-carboxylic acid methyl ester [ No CAS ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 4897 - 4901.

13
[ 116632-23-6 ]
[ 112-27-6 ]
[ 318262-05-4 ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

14
[ 116632-23-6 ]
[ 100-39-0 ]
[ 128923-99-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate; In acetone; at 20℃; for 2h;	3-Benzyloxy-5-bromo-nitrobenzeneTo an ice-cold solution of <strong>[116632-23-6]3-bromo-5-nitro-phenol</strong> (21.0 g, 96.33 mmol) in acetone (420.0 mL) was added K2CO3 (40.0 g, 289.41 mmol) followed by addition of benzyl bromide (17.20 mL, 144.40 mmol). The resulting reaction mixture was stirred at room temperature for 2 h. The reaction mixture was then diluted with water and extracted with EtOAc (3 x 250.0 mL). The combined organics was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude was purified over silica gel (100-200 M, 5percent EtOAc-Hexane) to get the desired product (27.0 g, 91percent). 1H-NMR (400 MHz, DMSO-d6): delta 5.13 (s, 2H), 7.35-7.45 (m, 6H), 7.75 (s, 1 H) and 7.98 (s, 1 H).
51%	With potassium carbonate; In acetone; for 3h;Reflux; Industry scale;	To a solution of <strong>[116632-23-6]3-bromo-5-nitro-phenol</strong> (770 g, 3.53 mol) in acetone (10 L) was added pulverized K2CO3 (2.45 kg, 17.75 mol) in one portion at rt followed by addition of benzyl bromide (632 mL, 5.32 mol) over a period of 30 min. The resulting reaction mixture was stirred for 15 min then heated at reflux for 3 h. After reaction completion (by TLC), the reaction mixture was filtered through celite and the acetone distilled off. The crude residue thus obtained was purified over silica gel (60-120 M) using EtOAc:hexane (5:95) to obtain the desired product (551 g, 51percent).
51%	With potassium carbonate; In [(2)H6]acetone; at 20℃; for 3.25h;Reflux;	To a solution of ii (770 g, 3.53 mol) in acetone (10 L) was added K2CO3 (2.45 kg, 17.75 mol) at RT followed by benzyl bromide (632 mL, 5.32 mol) over a period of 30 min. The mixture was stirred for 15 min and then heated at reflux for 3 h. The mixture was filtered through celite and the acetone was distilled off. The residue was purified over silica eluting with EtOAc:hexane (5:95) to obtain iii (551 g, 51percent).

References: [1]Patent: WO2007/148093,2007,A1 .Location in patent: Page/Page column 76-77.
[2]Patent: US2012/88750,2012,A1 .Location in patent: Page/Page column 14; 15.
[3]Patent: US2013/252938,2013,A1 .Location in patent: Paragraph 0428.
[4]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6598 - 6603.

15
[ 6311-60-0 ]
[ 116632-23-6 ]

References: [1]Tetrahedron Letters,2006,vol. 47,p. 4897 - 4901.

16
[ 116632-23-6 ]
[ 318262-07-6 ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

17
[ 116632-23-6 ]
C₁₆H₂₆BrN₃O₄ [ No CAS ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

18
[ 116632-23-6 ]
[ 318262-12-3 ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

19
[ 116632-23-6 ]
C₂₀H₂₉N₃O₅ [ No CAS ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

20
[ 116632-23-6 ]
C₂₁H₃₅N₃O₄Si [ No CAS ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

21
[ 116632-23-6 ]
C₂₃H₃₇N₃O₅Si [ No CAS ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

22
[ 116632-23-6 ]
[ 318262-14-5 ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.
[2]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

23
[ 116632-23-6 ]
C₃₆H₄₇N₃O₁₀ [ No CAS ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.
[2]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

24
[ 116632-23-6 ]
C₃₉H₅₅N₃O₁₀Si [ No CAS ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.
[2]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

25
[ 116632-23-6 ]
C₆₈H₈₃N₃O₂₀ [ No CAS ]

References: [1]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.
[2]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.
[3]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.
[4]Journal of the American Chemical Society,2000,vol. 122,p. 11315 - 11319.

26
[ 116632-23-6 ]
C₇₁H₉₁N₃O₂₀Si [ No CAS ]

27
[ 586-11-8 ]
[ 116632-23-6 ]

References: [1]Chemische Berichte,1909,vol. 42,p. 2192.

28
[ 586-10-7 ]
[ 116632-23-6 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1908,vol. 27,p. 36.

29
[ 116296-08-3 ]
[ 116632-23-6 ]

References: [1]Chemische Berichte,1909,vol. 42,p. 2192.

30
[ 116632-23-6 ]
[ 22615-51-6 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1968,vol. 87,p. 1327 - 1338.

31
[ 762-49-2 ]
[ 116632-23-6 ]
3-bromo-5-fluoroethoxynitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N-methyl-acetamide; hexane;	Step D 3-Bromo-5-fluoroethoxynitrobenzene A solution of <strong>[116632-23-6]3-bromo-5-nitrophenol</strong>, as described above in Step C, (1.04 g, 4.77 mmol) in dimethylformamide (30 mL) was cooled to 0 C. and treated with cesium carbonate (7.8 g, 23.8 mmol) giving an opaque red mixture. This mixture was treated with 1-bromo-2-fluoroethane (0.71 mL, 9.54 mmol) and the reaction was stirred overnight as the ice bath warmed to room temperature. The reaction was diluted with ethyl acetate/brine/aqueous saturated NH4Cl, the layers were separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, dried (MgSO4), filtered and concentrated in vacuo to give an orange brown oil. This material was purified by radial, thin layer chromatography (hexane to 10:1 hexane: ethyl acetate) to give 3-bromo-5-fluoroethoxynitrobenzene as a clear yellow liquid. 1H NMR (delta, CDCl3): 8.01 (1H, m), 7.71 (1H, m), 7.43 (1H, m), 4.88-4.69 (2H, m), 4.36-4.24 (2H, m); MS (m/z) 266, 264; mp 59-61 C.

References: [1]Patent: US6458935,2002,B1 .

32
[ 75-30-9 ]
[ 116632-23-6 ]
[ 915156-10-4 ]

Yield	Reaction Conditions	Operation in experiment
95.9%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	Example 1.81.8(1) Preparation of Intermediate A solution of <strong>[116632-23-6]3-bromo-5-nitrophenol</strong> (CAS 116632-23-6)(16 g, 73.39 mmol), 2-iodopropane (14.68 ml, 146.79 mmol) and K2CO3 (20.29 g, 146.79 mmol) in DMF (80 ml) was stirred overnight at room temperature. The reaction mixture was poured into water and AcOEt. The organic layer was washed with water then brine, dried over MgSO4, filtered and the solvent was evaporated to give 18.3 g (95.9percent) of intermediate shown
95.9%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	A solution of <strong>[116632-23-6]3-bromo-5-nitrophenol</strong> (16 g, 73.39 mmol), 2-iodopropane (14.68 ml, 146.79 mmol) and K2CO3 (20.29 g, 146.79 mmol) in DMF (80 ml) was stirred overnight at room temperature. The reaction mixture was poured into water and AcOEt. The organic layer was washed with water then brine, dried over MgSO4, filtered and the solvent was evaporated to give 18.3 g (95.9percent) of intermediate shown.
90%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	A mixture of compound 99 (4.36 g, 20.0 mmol), K2CO3 (5.5 g, 40.0 mmol), and 2-iodopropane (4.0 mL, 40.0 mmol) in DMF (20 mL) was stirred at room temperature overnight. The solution was diluted with ethyl acetate and washed with water and brine, dried over MgSO4, and the volatile was removed under reduced pressure. The residue was purified by column chromatography to yield the desired product (4.7 g, 90percent); 1H NMR (500 MHz, CDCl3): delta 1.38 (d, 6H, J= 6.0 Hz), 4.62 (septet, IH, J= 6.0 Hz), 7.33 (t, IH, J= 2.0 Hz), 7.64 (t, IH5 J= 2.1 Hz), 7.91 (t, IH, J= 1.8 Hz); 13C NMR (125 MHz, CDCl3): delta 21.9, 71.7, 109.3, 118.7, 123.1, 125.4, 149.7, 159.2; HRMS (FAB) calcd for C9H10BrNO3 (M+) 258.9844, found 258.9829.

References: [1]Patent: US2012/35171,2012,A1 .Location in patent: Page/Page column 52.
[2]Patent: US2012/41000,2012,A1 .Location in patent: Page/Page column 33.
[3]Patent: WO2006/125208,2006,A1 .Location in patent: Page/Page column 123.

33
[ 915156-09-1 ]
[ 116632-23-6 ]

Yield	Reaction Conditions	Operation in experiment
85%		Compound 98 (33.0 g, 0.14 mol) was treated with sulfuric acid (13.7 mL) and was refluxed in EtOH (550 mL) for 0.5 hours, followed by addition OfNaNO2 (23.8 g, 0.35 mol). The resulting mixture was refluxed for additional 1 hour and the volatile was evaporated. The residue was taken up with ethyl acetate and water. The layers were separated and the organic layer was washed with water, saturated sodium bicarbonate, and brine. After removal of solvent, the residue was purified by column chromatography on silica gel to afford the title compound (26 g, 85percent); 1H NMR (500 MHz, CD3OD): delta 5.00 (brs, IH), 7.58 (dd, IH, J= 1.7, 2.3 Hz), 7.47 (t, IH, J= 2.1 Hz), 7.69 (t, IH5 J= 1.9 Hz); 13C NMR (125 MHz, CD3OD): delta 110.5, 118.1, 123.7, 125.6, 151.0, 160.5; HRMS (FAB) calcd for C6H4BrNO3 (M+) 216.9375, found 216.9374.
85%		75.6 g (0.32 mmol) of 2-amino-3-bromo-5-nitrophenol prepared in Step 208 1) was dissolved in 1.5 L of 20 ethanol. The mixture was cooled to a temperature of ?10° C. 62.3 mL (1.17 mmol) of 21 sulfuric acid was added thereto at a temperature in a range of ?10° C. to ?2° C. for 30 minutes. The temperature of the reaction mixture was raised to 50° C., and 22 sodium nitrite was slowly added thereto for 30 minutes. The temperature of the reaction mixture was raised to 80° C., and the mixture was stirred under reflux for 3 hours. Once the reaction was complete, a solvent was removed therefrom under reduced pressure, and 11 water and 23 ethyl acetate were added dropwise thereto. An organic layer was extracted therefrom three times, and then washed with saline water. The organic layer was dried using anhydrous sodium sulfate, and then concentrated under reduced pressure. The obtained residue was purified using column chromatography (ethyl acetate:hexane=0.5:10 (v/v)), and the resulting solution was concentrated under reduced pressure to thereby obtain 60 g of a desired compound at a yield of 85percent. (0388) 1H-NMR (300 MHz, DMSO-d6): delta 10.90 (s, 1H), 7.75 (s, 1H), 7.51 (s, 1H), 7.36 (s, 1H).
84%	With sulfuric acid; sodium nitrite; In ethanol; at -10 - 55℃; for 3h;Reflux;	To a cooled solution (-10° C.) of i (643 g, 2.76 mol) in EtOH (13 L) was added conc. H2SO4 (515 mL, 9.97 mol) over a period of 35 min at -10 to -2° C. The mixture was allowed to warm to RT and then heated to 50-55° C. followed by the portion-wise addition of NaNO2 (671 g, 9.72 mol) over 30 min and the mixture heated at reflux for 3 h. The mixture was concentrated to 3 L and cooled to 0° C. followed by the addition of H2O (5 L) and extraction with EtOAc (3*6 L). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was treated with 25percent ether-hexane mixture (6 L) and stirred for 1 h, filtered and the solid and washed with hexane (3 L) to obtain ii (505 g, 84percent).

82%		3-Bromo-5-nitro-phenolTo an ice-cold solution of 2-amino-3-bromo-5-nitro-phenol (6.50 g, 27.89 mmol) in EtOH (150.0 mL) was added concentrated H2SO4 (9.40 mL, 177.13 mmol) portion wise. The reaction mixture was then heated to 5O0C followed by portion wise addition of NaNO2 (6.19 g, 89.82 mmol). The resulting solution was refluxed at 8O0C for 2 h. The reaction mixture was then diluted with water and extracted with EtOAc (3 x 150.0 mL). The combined organics was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude was purified over silica gel (100-200 M, 10percent EtOAc-Hexane) to get the desired product (5.0 g, 82percent).1H-NMR (400 MHz, DMSO-d6): delta 7.37 (s, 1 H), 7.53 (s, 1 H), 7.77 (s, 1 H) and 10.91 (s, 1 H).
	With sulfuric acid; sodium nitrite; In ethanol; at -10 - 55℃;	To a cooled solution (-10° C.) of 2-amino-3-bromo-5-nitro-phenol (643 g, 2.76 mol) in EtOH (13 L) was added conc. H2SO4 (515 mL, 9.97 mol) over a period of 35 min at -10 to -2° C. The reaction mixture was allowed to warm to rt then heated to 50-55° C. followed by portion-wise addition of NaNO2 (671 g, 9.72 mol) over 30 min then heated at reflux for 3 h. After completion of reaction (by TLC), the mixture was concentrated to 3 L and cooled to 0° C. followed by the addition of chilled water (5 L) and extraction with EtOAc (3.x.6 L). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a semi-solid residue. The residue was treated with 25percent ether-hexane mixture (6 L) and stirred for 1 h. The solid was filtered and washed with hexane (3 L) to obtain the desired product (505 g, 84percent).

References: [1]Patent: WO2006/125208,2006,A1 .Location in patent: Page/Page column 123.
[2]Patent: US2019/31643,2019,A1 .Location in patent: Paragraph 0386-0388.
[3]Patent: US2013/252938,2013,A1 .Location in patent: Paragraph 0427.
[4]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6598 - 6603.
[5]Patent: WO2007/148093,2007,A1 .Location in patent: Page/Page column 76-77.
[6]Patent: US2012/88750,2012,A1 .Location in patent: Page/Page column 14; 15.

34
[ 116632-23-6 ]
[ 96-32-2 ]
[ 1036756-48-5 ]

Yield	Reaction Conditions	Operation in experiment
		To the reaction mixture of <strong>[116632-23-6]3-bromo-5-nitrophenol</strong> (7.0 g, 32.1 mmol) in 30 ml of DMF add K2CO3 (9.8 g, 70.6 mmol) and stir for 3-5 minutes. To the reaction mixture add methyl 2-bromoacetate (5.4 g, 35.3 mmol) and stir at room temperature 18 hours or until done by LC. To the crude reaction add 450 ml of ethyl acetate and wash with saturated Na2CO3, water (3x), saturated NaCl, dried Na2SC^, filtered and concentrated in vaccuo to give crude, methyl 2-(3-bromo-5-nitrophenoxy)acetate, (9.0 g).

References: [1]Patent: WO2009/153313,2009,A1 .Location in patent: Page/Page column 250.

35
[ 116632-23-6 ]
[ 761446-44-0 ]
[ 1036756-65-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; water; at 80℃; for 1.5h;	The product from step 1 (1.0 eq) was dissolved in THF to make a 0.30 M solution. A 2.0 M aqueous solution of sodium carbonate (3.5 eq) was added. The mixture was degassed by bubbling argon through the solution for 10 min. 1 - Methylpyrazole-4-boronic acid, pinacol ester (1.2 eq) and (dppf)Pd(II)Cl2-CH2C12 (0.060 eq) were added. The mixture was stirred at 80 C for 90 min and then returned to ambient temperature. The mixture was diluted with ethyl acetate. Dilute aqueous hydrochloric acid was added until the pH of the aqueous layer was 5-6. The layers were separated. The aqueous phase was extracted with additional ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography (ethyl acetate then 92:8 ethyl acetate: methanol) to give the desired product as a yellow-brown solid. ES/MS m/z 220.0 (MH+).

References: [1]Patent: WO2009/153313,2009,A1 .Location in patent: Page/Page column 181.

Historical Records

Technical Information

• Acidity of Phenols • Alkyl Halide Occurrence • Chan-Lam Coupling Reaction • Electrophilic Substitution of the Phenol Aromatic Ring • Etherification Reaction of Phenolic Hydroxyl Group • General Reactivity • Grignard Reaction • Halogenation of Phenols • Hiyama Cross-Coupling Reaction • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Oxidation of Phenols • Pechmann Coumarin Synthesis • Preparation of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Dihalides • Reimer-Tiemann Reaction • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling

Related Functional Groups of
[ 116632-23-6 ]

Aryls

A141768 [16618-67-0]

1-Bromo-3-methoxy-5-nitrobenzene

Similarity: 0.95

A170954 [52427-05-1]

2-Bromo-5-nitrophenol

Similarity: 0.93

A215987 [5847-59-6]

2-Bromo-4-nitrophenol

Similarity: 0.91

A135322 [27684-84-0]

5-Bromo-2-nitrophenol

Similarity: 0.90

A162176 [101935-40-4]

2-Bromo-3-nitrophenol

Similarity: 0.88

Bromides

A141768 [16618-67-0]

1-Bromo-3-methoxy-5-nitrobenzene

Similarity: 0.95

A170954 [52427-05-1]

2-Bromo-5-nitrophenol

Similarity: 0.93

A215987 [5847-59-6]

2-Bromo-4-nitrophenol

Similarity: 0.91

A135322 [27684-84-0]

5-Bromo-2-nitrophenol

Similarity: 0.90

A162176 [101935-40-4]

2-Bromo-3-nitrophenol

Similarity: 0.88

Nitroes

A141768 [16618-67-0]

1-Bromo-3-methoxy-5-nitrobenzene

Similarity: 0.95

A170954 [52427-05-1]

2-Bromo-5-nitrophenol

Similarity: 0.93

A215987 [5847-59-6]

2-Bromo-4-nitrophenol

Similarity: 0.91

A135322 [27684-84-0]

5-Bromo-2-nitrophenol

Similarity: 0.90

A162176 [101935-40-4]

2-Bromo-3-nitrophenol

Similarity: 0.88

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.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
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.
P331	Do NOT induce vomiting.
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.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
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
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

{[proInfo.proName]}

CAS No.: 116632-23-6

{[proInfo.proName]}