[ CAS No. 189035-22-1 ] {[proInfo.proName]}

Name: 189035-22-1|6-Bromo-2,3-dihydrobenzofuran|95%
Brand: Ambeed
SKU: A118810
Rating: 92 (40 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

2D 3D

Structure of 189035-22-1 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 189035-22-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 189035-22-1 ]

SDS Specification

Alternatived Products of [ 189035-22-1 ]

Product Details of [ 189035-22-1 ]

CAS No. :	189035-22-1	MDL No. :	MFCD08704305
Formula :	C₈H₇BrO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BQWBDYZMUCSEHK-UHFFFAOYSA-N
M.W :	199.05	Pubchem ID :	11252616
Synonyms :

Safety of [ 189035-22-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 189035-22-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 189035-22-1 ]
Downstream synthetic route of [ 189035-22-1 ]

[ 189035-22-1 ] Synthesis Path-Upstream 1~8

1
[ 377091-18-4 ]
[ 189035-22-1 ]

Yield	Reaction Conditions	Operation in experiment
94%	With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 4 h;	nBuLi (2.5 M in hexane, 5.13 ml_, 12.84 mmol) was added to a -78°C cooled solution of 1 ,4-dibromo-2-(2-bronnoethoxy)benzene (3.84 g, 10.70 mmol) in THF (100 ml_). The reaction mixture was stirred at low temperature for 4 h. It was poured into H₂O (100 ml_) and extracted with EtOAc (2x100 ml_). The organic layer was dried over Na₂SO₄ (anhydrous), filtered and concentrated. The crude residue was purified by flash chromatography on SiO₂ (3percentEtOAc/hexanes) to furnish 6-bromo-2,3-dihydro-1-benzofuran (2. g, yellow solid, yield: 94percent).
85%	With n-butyllithium In tetrahydrofuran; benzene at -78℃; for 1 h; Inert atmosphere	To a solution of 1,4-dibromo-2-(2-bromoethoxy) benzene (2.13 g, 5.9 mmol) in benzene / tetrahydrofuran (28 mL, 2:5) at -78°C under N₂ was added n-butyllithium (2.5 mL, 6.1 mmol). The mixture was stirred at -78°C for 1 h, and quenched by acetic acid. Water was added, and the organic layer was seperated, dried, and concentrated under vacuum to give the title compound (1.00 g, 85 percent). ¹H NMR (CDCl₃): δ 7.03 (1H, d, J = 8.0 Hz), 6.91-6.93 (2H, m), 4.58 (2H, t, J = 4.8 Hz), 3.15 (2H, t, J = 4.8 Hz)
85%	With n-butyllithium In tetrahydrofuran; benzene at -78℃; for 1 h; Inert atmosphere	To a solution of 1,4-dibromo-2-(2-bromoethoxy) benzene (2.13 g, 5.9 mmol) in benzene/ tetrahydrofuran (28 mL, 2:5) at −78° C. under N2 was added n-butyllithium (2.5 mL, 6.1 mmol). The mixture was stirred at −78° C. for 1 h, and quenched by acetic acid. Water was added, and the organic layer was seperated, dried, and concentrated under vacuum to give the title compound (1.00 g, 85percent). 1H NMR (CDCl3) δ7.03 (1H, d, J=8,0 Hz), 6.91-6.93 (2H, m), 4.58 (2H, t, J=4.8 Hz), 3.15 (2H, t, J=4.8 Hz).

79%	With n-butyllithium In tetrahydrofuran; hexane at -78 - 0℃; for 2.5 h; Inert atmosphere	1.6 M n-Butyllithium/hexane solution (21.84 mL, 34.94 mmol) was slowly added to a solution of 1,4-dibromo-2-(2-bromoethoxy)benzene (10.45 g, 29.12 mmol) in THF (200 mL) at-78°C under argon gas atmosphere. The reaction mixture was stirred at -78°C for 30 min, and then at 0°C for 2 hr. The reaction mixture was added to ice water, and 2N hydrochloric acid was added thereto until the pH of the mixture became 3. Then, the mixture was extracted three times with a mixed solvent of ethyl acetate/hexane (3:1). The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 2→8percent ethyl acetate/hexane) to give 6-bromo-2,3-dihydrobenzofuran (4.57 g, 22.96 mmol, 79percent) as a white solid.
9.4 g	With n-butyllithium In tetrahydrofuran; hexaneInert atmosphere; Cooling	To a solution of 1,4-dibromo-2-(2-bromoethoxy)benzene (22.3 g, 62.2 mmol) in THF (180 mL) was added 1.57 M n-BuLi in hexanes (40 mL, 62.8 mmol) under Ar at -76 °C. After stirring at -76 °C overnight, the mixture was quenched with sat. NH₄Cl aq and extracted with AcOEt. The organic phase was washed with brine and dried over Na₂SO₄. After filtration and evaporation, the residue was recrystallized from ethanol (28 mL) and water (3 mL) to obtain 7 as a white solid (9.4 g, 76percent). ¹H NMR (400 MHz, CDCl₃) δ = 7.03 (d, J = 7.6 Hz, 1H), 6.97 (d, J = 1.6 Hz, 1H), 6.94 (dd, J = 1.6, 7.6 Hz, 1H), 4.59 (t, J = 8.8 Hz, 2H), 3.15 (t, J = 8.8 Hz, 1H); MS (ESI+) 200.1 (M+H)⁺.

Reference： [1] Patent: WO2009/7399, 2009, A1, . Location in patent: Page/Page column 86
[2] Patent: EP2862571, 2015, A1, . Location in patent: Paragraph 0146; 0147
[3] Patent: US2015/166559, 2015, A1, . Location in patent: Paragraph 0200; 0201
[4] Patent: TW2016/2105, 2016, A, . Location in patent: Paragraph 1108
[5] Patent: US2010/16297, 2010, A1, . Location in patent: Page/Page column 34
[6] Patent: US2011/263612, 2011, A1, . Location in patent: Page/Page column 165
[7] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 15, p. 4792 - 4803

2
[ 377091-17-3 ]
[ 189035-22-1 ]

Yield	Reaction Conditions	Operation in experiment
40%	Stage #1: With phosphorus tribromide In toluene at 90℃; for 2.5 h; Heating / reflux Stage #2: With sodium hydroxide In water; toluene at 20℃; Stage #3: With n-butyllithium In tetrahydrofuran; hexane at -75℃; for 0.5 h;	2-(2,5-dibromophenoxy)ethanol (4.65 g, 15.7 mmol) was dissolved in toluene (33 mL) with stirring under N₂. PBr₃ (0.67 mL, 7.07 mmol) was added and the resulting mixture heated at 90 ⁰C under reflux condenser under N₂ for 2.5 hours. The mixture was cooled to room temperature with a H₂O bath and IN NaOH (28 mL) was added. The mixture was diluted with Et₂O, shaken, and the layers separated. The organics were washed with H₂O, dried over MgSO₄, filtered, and concentrated on a rotary evaporator. The resulting oil was dissolved in THF (15 mL) with stirring under N₂. The solution was cooled to -75 ⁰C and n-BuLi (9.82 mL of a 1.6 M solution in hexane, 15.7 mmol) was added dropwise. The resulting clear, colorless solution was stirred 30 minutes at -75 ⁰C, and then HOAc (1 mL) was added. The resulting mixture was warmed to room temperature and partitioned between H2O and Et₂O. The organics were washed once with 0.5 M NaOH, once with H₂O, and concentrated on a rotary evaporator. Flash chromatography <n="145"/>(5-10percent EtOAc/hexane) gave 1.38 g (90percent purity) (40percent yield) of 6-bromo-2,3- dihydrobenzofuran as a white solid. R_f= 0.56 (30percent EtOAc/hexane). ¹H NMR (300 MHz, DMSO-D6) δ ppm 3.13 (t, J=8.52 Hz, 2 H) 4.56 (t, J=8.79 Hz, 2 H) 6.95 - 7.01 (m, 2 H) 7.14 - 7.20 (m, 1 H).

Reference： [1] Patent: WO2007/84560, 2007, A2, . Location in patent: Page/Page column 143-144
[2] Patent: EP2862571, 2015, A1,
[3] Patent: US2015/166559, 2015, A1,
[4] Patent: TW2016/2105, 2016, A,

3
[ 496-16-2 ]
[ 189035-22-1 ]

Reference： [1] Journal of Medicinal Chemistry, 2003, vol. 46, # 22, p. 4790 - 4798

4
[ 1435-52-5 ]
[ 189035-22-1 ]

Reference： [1] Patent: EP2862571, 2015, A1,
[2] Patent: US2015/166559, 2015, A1,
[3] Patent: TW2016/2105, 2016, A,

5
[ 28165-52-8 ]
[ 189035-22-1 ]

Reference： [1] Patent: US2011/263612, 2011, A1,

6
[ 97674-02-7 ]
[ 189035-22-1 ]
[ 374706-07-7 ]

Yield	Reaction Conditions	Operation in experiment
73.7%	With bis-triphenylphosphine-palladium(II) chloride In toluene at 90℃; for 16 h;	The title compound was prepared according to procedures reported in the literature and known by persons skill in the art, using 6-bromo-2,3-dihydro-1-benzofuran (1 g, 5.03 mmol) as starting material. In a preferred method, 6-bromo-2,3-dihydro-1-benzofuran (1 g, 5.03 mmol) in toluene (10 mL) was degassed for 30 min. To this solution, 1-ethoxyvinyl tributyltin (2.012 g, 5.53 mmol) and bis(triphenylphosphine)palladium dichloride (0.35 g, 0.50 mmol) were added at rt and stirred for 16 hours at 90 °C. The reaction mixture was cooled to rt and filtered through celite. After evaporation of the solvent, 6 N HCl solution in water (10 mL) was added and the mixture was stirred for 1 hour at rt. It was concentrated and neutralized with sat. NaHCO₃. The desired product was extracted with DCM (50 mL), dried over Na₂SO₄ and concentrated. The crude product was purified by flash chromatography to give the title compound. Yield: 73.7percent (0.6 g, pale yellow solid). ¹H NMR (400 MHz, DMSO-d₆): δ 7.48 (d, J = 7.64 Hz, 1H), 7.37-7.35 (d, J = 7.68 Hz, 1H), 7.26 (s, 1H), 4.58 (t, J = 8.76 Hz, 2H), 3.24 (t, J = 8.76 Hz, 2H), 2.53 (s, 3H). LCMS: (Method A) 163.2 (M+H), Rt. 3.01 min, 97.60percent (Max).

Reference： [1] Patent: WO2017/144635, 2017, A1, . Location in patent: Page/Page column 32; 33

7
[ 189035-22-1 ]
[ 374706-07-7 ]

Reference： [1] Patent: WO2006/137796, 2006, A1,

8
[ 50-00-0 ]
[ 189035-22-1 ]
[ 1083168-69-7 ]

Yield	Reaction Conditions	Operation in experiment
74%	With tert.-butyl lithium In tetrahydrofuran; pentane at -74 - 20℃; Inert atmosphere	To a solution of 7 (4.29 g, 21.6 mmol) in THF (43 mL) was added 1.76 M t-BuLi in pentane (25.7 mL, 45.2 mmol) under Ar at -74 °C. Paraformaldehyde (0.97 g, 32.3 mmol) was added to the mixture at -74 °C and the mixture was stirred at room temperature overnight. The mixture was quenched with satd NH₄Cl aq and extracted with AcOEt. The organic layer was washed with brine and dried over MgSO₄, then filtered. After removal of the solvent, the residue was recrystallized from CH₂Cl₂ (6.5 mL) and n-hexane (25.9 mL) to obtain 8 as a pale red solid (2.39 g, 74percent). ¹H NMR (400 MHz, CDCl₃) δ = 7.16 (d, J = 7.2 Hz, 1H), 6.84 (d, J = 7.2 Hz, 1H), 6.81 (s, 1H), 4.63 (br s, 2H), 4.58 (t, J = 8.8 Hz, 2H), 3.20 (t, J = 8.8 Hz, 2H); MS (ESI+) 151.1 (M+H)⁺.

Reference： [1] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 15, p. 4792 - 4803