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[ CAS No. 108-37-2 ] {[proInfo.proName]}

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Chemical Structure| 108-37-2
Chemical Structure| 108-37-2
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Product Details of [ 108-37-2 ]

CAS No. :108-37-2 MDL No. :MFCD00000568
Formula : C6H4BrCl Boiling Point : -
Linear Structure Formula :- InChI Key :JRGGUPZKKTVKOV-UHFFFAOYSA-N
M.W : 191.45 Pubchem ID :7928
Synonyms :

Calculated chemistry of [ 108-37-2 ]

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 0.0
Num. H-bond donors : 0.0
Molar Refractivity : 39.15
TPSA : 0.0 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -4.84 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.24
Log Po/w (XLOGP3) : 3.7
Log Po/w (WLOGP) : 3.1
Log Po/w (MLOGP) : 3.64
Log Po/w (SILICOS-IT) : 3.22
Consensus Log Po/w : 3.18

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.91
Solubility : 0.0234 mg/ml ; 0.000122 mol/l
Class : Soluble
Log S (Ali) : -3.39
Solubility : 0.0779 mg/ml ; 0.000407 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.87
Solubility : 0.0259 mg/ml ; 0.000136 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 1.53

Safety of [ 108-37-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P305+P351+P338 UN#:N/A
Hazard Statements:H227-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 108-37-2 ]

* 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 [ 108-37-2 ]
  • Downstream synthetic route of [ 108-37-2 ]

[ 108-37-2 ] Synthesis Path-Upstream   1~40

  • 1
  • [ 110-85-0 ]
  • [ 108-37-2 ]
  • [ 6640-24-0 ]
Reference: [1] Tetrahedron Letters, 1996, vol. 37, # 26, p. 4463 - 4466
  • 2
  • [ 108-37-2 ]
  • [ 6640-24-0 ]
Reference: [1] Tetrahedron Letters, 2006, vol. 47, # 15, p. 2549 - 2552
[2] Patent: WO2011/28947, 2011, A2,
[3] Patent: WO2018/26371, 2018, A1,
  • 3
  • [ 108-37-2 ]
  • [ 541-41-3 ]
  • [ 7094-34-0 ]
Reference: [1] Organic Letters, 1999, vol. 1, # 13, p. 2077 - 2080
  • 4
  • [ 108-37-2 ]
  • [ 587-04-2 ]
  • [ 7094-34-0 ]
Reference: [1] Chemistry - A European Journal, 2006, vol. 12, # 6, p. 1648 - 1656
  • 5
  • [ 108-37-2 ]
  • [ 124-38-9 ]
  • [ 93224-85-2 ]
YieldReaction ConditionsOperation in experiment
85%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexanes at -78℃; for 2 h;
Stage #2: for 0.25 h;
Stage #3: With hydrogenchloride In tetrahydrofuran; hexanes; water
Step 1. 2-bromo-6-chlorobenzoic acid: To a - 78 0C solution of n-BuLi (10 niL, 25 mmol, 2.5M Hexanes) in anhydrous THF (70 rnL) was added diisopropylamine (3.5 rnL, 25 mmol). After stirring for 15 min, l-chloro-3- bromobenzene (4.32 g, 25 mmol) was added and stirred for 2 h at -78 0C. Dry ice (CO2) was added and after 15 min a 2N aq HCl solution (100 mL) was added. The reaction mixture was extracted with EtOAc. The product was re-crystallized from hexanes and isolated 5 g (85percent) of 2-bromo-6-chlorobenzoic acid.
Reference: [1] Organic Letters, 2009, vol. 11, # 5, p. 1051 - 1054
[2] Tetrahedron Letters, 1997, vol. 38, # 9, p. 1559 - 1562
[3] Patent: WO2008/124582, 2008, A1, . Location in patent: Page/Page column 117
[4] Patent: WO2008/124575, 2008, A1, . Location in patent: Page/Page column 108
[5] Organic Process Research and Development, 2005, vol. 9, # 6, p. 764 - 767
  • 6
  • [ 108-37-2 ]
  • [ 93224-85-2 ]
Reference: [1] Patent: EP1477482, 2004, A1, . Location in patent: Page 74
  • 7
  • [ 768-66-1 ]
  • [ 108-37-2 ]
  • [ 93224-85-2 ]
Reference: [1] Patent: US2003/220375, 2003, A1,
  • 8
  • [ 108-37-2 ]
  • [ 93224-85-2 ]
Reference: [1] Patent: US2003/220268, 2003, A1,
[2] Patent: US2003/220318, 2003, A1,
  • 9
  • [ 108-37-2 ]
  • [ 383-63-1 ]
  • [ 321-31-3 ]
YieldReaction ConditionsOperation in experiment
97.3%
Stage #1: With n-butyllithium In tetrahydrofuran at -78 - -50℃; for 1 h;
Stage #2: at -78 - 20℃;
Accurate weighing of m-chlorobromobenzene (3-chlorobromobenzene) (19.15 g, 0.1 mol) was dissolved in 100 ml of tetrahydrofuran and the ethanol-dry ice bath cooled the solution temperature to a negative 78 to negative 50 ° C. A solution of butyllithium (0.12 mol) was added dropwise and incubated for 1 hour at a negative 78 to negative temperature of 50 ° C. Then, ethyl trifluoroacetate (18.4 g, 0.13 mol) was added dropwise at this temperature. After completion of the dropwise addition, the mixture was withdrawn and the mixture was spontaneously stirred at room temperature. Then, hydrochloric acid (30 ml, 0.3 mol) was added dropwise, the layers were stirred, the organic layer was depressurized to remove the solvent. 20.7 g of crude 2,2,2-trifluoro-(3'-chlorophenyl)ethanone was obtained and distilled to give 20.3 g of a colorless transparent liquid, content of 95percent, yield 97.3percent.
Reference: [1] Patent: CN106518636, 2017, A, . Location in patent: Paragraph 0113; 0114; 0115; 0116; 0121; 0122; 0123; 0124
[2] Organic Letters, 2017, vol. 19, # 3, p. 588 - 591
  • 10
  • [ 340-07-8 ]
  • [ 108-37-2 ]
  • [ 321-31-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 5, p. 979 - 993
  • 11
  • [ 108-37-2 ]
  • [ 407-25-0 ]
  • [ 321-31-3 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1997, vol. 70, # 12, p. 3081 - 3090
  • 12
  • [ 108-37-2 ]
  • [ 353-85-5 ]
  • [ 321-31-3 ]
Reference: [1] Journal of medicinal chemistry, 1966, vol. 9, # 2, p. 176 - 178
  • 13
  • [ 108-37-2 ]
  • [ 360-92-9 ]
  • [ 321-31-3 ]
Reference: [1] Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 317 - 324[2] Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 2, p. 365 - 373
  • 14
  • [ 108-37-2 ]
  • [ 766-83-6 ]
Reference: [1] Organic and biomolecular chemistry, 2003, vol. 1, # 3, p. 498 - 506
[2] Journal of Sulfur Chemistry, 2011, vol. 32, # 1, p. 3 - 16
[3] European Journal of Organic Chemistry, 2016, vol. 2016, # 18, p. 3056 - 3059
  • 15
  • [ 108-37-2 ]
  • [ 1066-54-2 ]
  • [ 766-83-6 ]
Reference: [1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 39, p. 6707 - 6712
  • 16
  • [ 75-21-8 ]
  • [ 108-37-2 ]
  • [ 5182-44-5 ]
Reference: [1] Journal of the Chemical Society, 1964, p. 1548 - 1553
  • 17
  • [ 108-37-2 ]
  • [ 16799-05-6 ]
Reference: [1] Journal of the Chemical Society, 1964, p. 1548 - 1553
  • 18
  • [ 108-37-2 ]
  • [ 109-94-4 ]
  • [ 1128-76-3 ]
YieldReaction ConditionsOperation in experiment
74%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5 h;
Stage #2: at -78℃; for 3 h;
Stage #3: With ethanol; iodine; potassium carbonate In tetrahydrofuran; hexane at -78 - 20℃; for 14 h;
General procedure: n-BuLi (1.67 M solution in hexane, 1.32 mL, 2.2 mmol) was added dropwise into a solution of p-bromochlorobenzene (383 mg, 2.0 mmol) in THF (3 mL) at -78 °C for 30 min. Then, ethyl formate (1.6 mL, 20 mmol) was added to the mixture and the obtained mixture was stirred at -78 °C. After 3 h at the same temperature, I2 (1523 mg, 6 mmol), K2CO3 (1382 mg, 10 mmol) and EtOH (3 mL) were added at -78 °C and the mixture was stirred for 14 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (5 mL) and was extracted with CHCl3 (3.x.20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide ethyl 4-chlorobenzoate in 77percent yield. If necessary, the product was purified by short column chromatography (SiO2:hexane:EtOAc=9:1) to give pure ethyl 4-chloro-1-benzoate as a colorless oil.
Reference: [1] Tetrahedron, 2012, vol. 68, # 24, p. 4701 - 4709
  • 19
  • [ 108-37-2 ]
  • [ 1609-47-8 ]
  • [ 1128-76-3 ]
Reference: [1] Synthesis, 2004, # 4, p. 568 - 572
  • 20
  • [ 108-37-2 ]
  • [ 79-10-7 ]
  • [ 1866-38-2 ]
Reference: [1] Synlett, 2013, vol. 24, # 2, p. 254 - 258
  • 21
  • [ 590-28-3 ]
  • [ 108-37-2 ]
  • [ 67-63-0 ]
  • [ 101-21-3 ]
Reference: [1] Advanced Synthesis and Catalysis, 2012, vol. 354, # 13, p. 2443 - 2446,4
  • 22
  • [ 108-37-2 ]
  • [ 13101-40-1 ]
Reference: [1] Organic Letters, 2013, vol. 15, # 1, p. 140 - 143
  • 23
  • [ 108-37-2 ]
  • [ 63860-31-1 ]
  • [ 89465-97-4 ]
Reference: [1] Patent: US2002/173490, 2002, A1,
  • 24
  • [ 108-37-2 ]
  • [ 7697-37-2 ]
  • [ 63860-31-1 ]
  • [ 89465-97-4 ]
Reference: [1] Gazzetta Chimica Italiana, 1874, vol. 4, p. 341[2] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1875, p. 317
[3] Journal of the Chemical Society, 1928, p. 693
  • 25
  • [ 108-37-2 ]
  • [ 68-12-2 ]
  • [ 64622-16-8 ]
YieldReaction ConditionsOperation in experiment
80%
Stage #1: With magnesium chloride In 2-methyltetrahydrofuran
Stage #2: With lithium diisopropyl amide In tetrahydrofuran; 2-methyltetrahydrofuran; n-heptane at -78 - -75℃; for 1 h;
The thermal characteristics of this reaction were studied using an HEL Simular reaction calorimeter. The calorimeter was equipped with a double-jacketed, 0.8-liter, glass reactor (6 bars). The inner jacket contained a heat-transfer fluid and the outer jacket was evacuated to insulate the system. A quantity of 26.5 g (0.139 moles, 1 equivalent) of 3-bromochlorobenzene (10), 200 ml of 2-methyltetrahydrofuran (Me-THF) and 15.0 g (0.158 moles, 1.1 equivalents) of anhydrous magnesium chloride was charged to this reactor. The slurry was then cooled to -78° C. A quantity of 91.2 ml (0.158 moles, 1.3 equivalents) of lithium diisopropylamide (LDA, 2M in heptane/THF) was charged into the batch, keeping the temp <--75° C. The batch was held for an hour after LDA addition. A quantity of 15.0 ml (0.194 moles, 1.4 equivalents) of N,N-dimethylformamide was charged into the batch at -78° C., keeping the temperature <--75° C. The mixture was stirred for an hour and gradually warmed to 0° C. At 0° C., the reaction was quenched with 150 ml of 0.5M citric acid solution. The layers were separated and the organic layer was collected and concentrated to dryness. The desired product (12) was isolated in 80percent yield and 99percent purity by GC.
59%
Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -70℃; for 1 h;
Stage #2: at -70℃; for 1 h;
i).
Preparation of 2-bromo-6-chlorobenzaldehyde (i-5b)
To a solution of 1-bromo-3-chlorobenzene (i-5a) (5 g, 26. mmol) in THF (50 mL) was added LDA (1 M, 31.3 mL, 8.7 mmol) dropwise via an addition funnel at -70° C.
The mixture was stirred at -70° C. for 1 h. DMF (2.87 mL, 39.1 mmol, 227 mmol) in THF (20 mL) was added dropwise maintaining the internal temperature below -70° C.
The reaction was stirred vigorously at -70° C. for 1 h.
Warmed to -30° C., the reaction was poured into 1 M HCl (100 mL) partitioned between water (10 mL) and DCM (30 mL).
The aqueous layer was extracted with DCM (20 mL*3).
The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo to afford the title compound (3.6 g, yield: 59percent). LCMS (ESI) calc'd for C7H4BrClO [M+H]+: 219. found: 219.
53%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexanes at -78 - 0℃; for 1.16667 h;
A 1.6 molar solution of butyllithium in hexanes (4.5 mL, 2.8 mmol) was placed in a three-neck flask equipped with a STIRRER, addition funnel, low-temperature thermometer and nitrogen inlet tube at 0 °C. A solution of diisopropyl amine (1.13 mL, 8.1 mmol) in anhydrous tetrahydrofuran was added dropwise. The resulting solution was stirred at 0 °C for ten minutes, then cooled to-78 °C. Upon cooling, a solution of L-BROMO-3- chlorobenzene (1.4 g, 7.3 mmol) in anhydrous tetrahydrofuran was added dropwise. The reaction was allowed to stir at-78 °C for one hour. Anhydrous dimethylformamide (636 GEL) was added. The solution was allowed to slowly warm to room temperature, followed by the addition of acetic acid (50 mL) and water (50 mL). The aqueous mixture was extracted with ether twice and the ether layers were separated. The combined ether layers were successively washed with aqueous hydrochloric acid and brine. The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 9: 1 hexanes: ethyl acetate to yield 2-chloro-6-bromobenzaldehyde as an off white solid (850 mg, 53 percent yield). NMR (300 MHz, CDC13): 10.4 (s, 1H), 7.6 (m, 1H), 7.45 (m, 1H), 7.3 ppm (m, 1H).
3.6 g
Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -70℃; for 1 h;
Stage #2: for 1 h;
Preparation of 2-bromo-6-chlorobenzaldehyde (i-5b). To a solution of l-bromo-3-chlorobenzene (i-5a) (5 g, 26. mmol) in THF (50 mL) was added LDA (1 M, 31.3 mL, 8.7 mmol) dropwise via an addition funnel at -70 °C. The mixture was stirred at -70 °C for 1 h. DMF (2.87 mL, 39.1 mmol, 227 mmol) in THF (20 mL) was added dropwise maintaining the internal temperature below -70 °C. The reaction was stirred vigorously at -70 °C for 1 h. Warmed to -30 °C, the reaction was poured into 1 M HCl (100 mL) partitioned between water (10 mL) and DCM (30 mL). The aqueous layer was extracted with DCM (20 mL x 3). The combined organic layers were dried over anhydrous Na2S04 and concentrated in vacuo to afford the title compound (3.6 g, yield: 59 percent). LCMS (ESI) calc'd for C7H4BrC10 [M+H]+: 219, found: 219.

Reference: [1] Organic Process Research and Development, 2014, vol. 18, # 1, p. 228 - 238
[2] Patent: US2009/118546, 2009, A1, . Location in patent: Page/Page column 6
[3] Patent: US2015/210687, 2015, A1, . Location in patent: Paragraph 0244
[4] Patent: WO2004/99164, 2004, A1, . Location in patent: Page 62-63; 21/22
[5] Journal of Heterocyclic Chemistry, 2018, vol. 55, # 3, p. 670 - 684
[6] Patent: WO2014/28591, 2014, A2, . Location in patent: Page/Page column 45
  • 26
  • [ 108-37-2 ]
  • [ 63503-60-6 ]
YieldReaction ConditionsOperation in experiment
57%
Stage #1: With n-butyllithium In tetrahydrofuran; hexaneInert atmosphere
Stage #2: With Trimethyl borate In tetrahydrofuran; hexaneInert atmosphere
General procedure: Under an argon atmosphere a solution of the appropriate bromobenzene (1 equivalent) dissolved in anhydrous THF (approximately 30 mL per mmol bromobenzene) is cooled to -78 °C using a nitrogen-ethanol-bath. A solution of 2.3 equivalents of n-butyllithium in hexane is added drop wise keeping the temperature below -78 °C. After completion the mixture is stirred for one hour at this temperature. Then 1.5 equivalents of trimethyl borate are added slowly and the reaction mixture is stirred at -78 °C for another hour. The cooling bath is then removed, the reaction mixture is stirred until room temperature is reached and quenched with a saturated solution of ammonium chloride. THF and the major part of the water is removed under reduced pressure, the residue is laced with 3M hydrochloric acid until a pH of 3 is reached. After extraction with DCM (3 x) the organic phases are collected, washed with brine, dried over sodium sulphate and filtered. DCM is removed under reduced pressure, the resulting solid is washed first with ice cold water and then with PE and dried.
Reference: [1] European Journal of Medicinal Chemistry, 2017, vol. 126, p. 590 - 603
[2] Organic Letters, 2005, vol. 7, # 21, p. 4757 - 4759
[3] Tetrahedron, 2007, vol. 63, # 35, p. 8529 - 8536
  • 27
  • [ 108-37-2 ]
  • [ 121-43-7 ]
  • [ 63503-60-6 ]
Reference: [1] Organic Letters, 2016, vol. 18, # 15, p. 3630 - 3633
  • 28
  • [ 108-37-2 ]
  • [ 13283-31-3 ]
  • [ 63503-60-6 ]
Reference: [1] Journal of Organometallic Chemistry, 1983, vol. 259, # 3, p. 269 - 274
  • 29
  • [ 108-37-2 ]
  • [ 56962-04-0 ]
YieldReaction ConditionsOperation in experiment
81%
Stage #1: With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In hexane at 20℃; for 18 h; Inert atmosphere
Stage #2: With Oxone In water; acetone for 0.166667 h;
a.
3-Bromo-5-chloro-phenol (Intermediate 62a)
A flask containing (1,5-cyclooctadiene)(methoxy)-iridium(I) dimer (84 mg, 0.13 mmol), 4,4'-di-tert butyl-2-2'-dipyridyl (69 mg, 0.26 mmol) and bis(pinacolato)diboron (1.29 g, 5.11 mmol) was purged with Ar, then hexanes (26 mL) and 1-bromo-3-chlorobenzene (1 mL, 8.51 mmol) were added sequentially.
The solution was stirred at RT for 18 h.
The reaction mixture was concentrated in vacuo, re-dissolved in acetone (26 mL), then oxone (5.23 g, 8.51 mmol) in water (26 mL) added [Caution: exotherm observed].
After 10 min, the reaction mixture was diluted with DCM.
The layers separated, and the aqueous layer extracted with DCM.
The combined organics were washed with brine, dried and concentrated in vacuo to give the title compound (1.43 g, 81percent). LCMS (Method 3): Rt 3.74 min, m/z 205, 207 [M-H+].
81%
Stage #1: With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In hexane at 20℃; for 18 h; Inert atmosphere
Stage #2: With Oxone In water; acetone for 0.166667 h;
A flask containing (l,5-cyclooctadiene)(methoxy)-iridium(I) dimer (84 mg, 0.13 mmol), 4,4'-di-tert butyl-2-2'-dipyridyl (69 mg, 0.26 mmol) and bis(pinacolato)diboron (1.29 g, 5.11 mmol) was purged with Ar, then hexanes (26 mL) and l-bromo-3- chlorobenzene (1 mL, 8.51 mmol) were added sequentially. The solution was stirred at RT for 18 h. The reaction mixture was concentrated in vacuo, re-dissolved in acetone (26 mL), then oxone (5.23 g, 8.51 mmol) in water (26 mL) added [Caution: exotherm observed]. After 10 min, the reaction mixture was diluted with DCM. The layers separated, and the aqueous layer extracted with DCM. The combined organics were washed with brine, dried and concentrated in vacuo to give the title compound (1.43 g, 81percent). LCMS (Method 3): Rt 3.74 min, m/z 205, 207 [M-H+].
62%
Stage #1: at 150℃; for 3.5 h; Inert atmosphere
Stage #2: With Oxone; water In acetoneCooling with ice
3-Bromo-5-chloro-phenol; Under an atmosphere of dry nitrogen, 103 mg 1 ,5-cyclooctadiene(H5-indenyl)iridium (I) was put in a 25 ml. Pyrex bottle. Subsequently were added 0.04 ml. 1 ,2-bis(dimethylphosphino)ethane, 0.61 ml. 3-bromochlorobenzene and 1.52 ml. pinacolborane. The mixture was stirred at 150°C for 3.5 h. After cooling to room temperature, the borane adduct was taken up in 17 ml. acetone to give a clear solution. This solution was added slowly to 17.41 ml. of a 0.30 M solution of oxone in water cooled in an ice bath. The mixture was stirred vigorously for 15 min. at room <n="47"/>temperature and extracted three times with DCM. The combined organic phases were dried over Na2SC>4 and evaporated to dryness. The residue was purified by flash chromatography (DCM) to yield 750 mg (62percent) of a beige solid. 1H NMR complies with known data (compound (1 ), Maleczka, 2003).
Reference: [1] Patent: US2014/364412, 2014, A1, . Location in patent: Paragraph 0683; 0684
[2] Patent: WO2014/195402, 2014, A1, . Location in patent: Page/Page column 217
[3] Patent: WO2009/115515, 2009, A1, . Location in patent: Page/Page column 44-45
[4] Journal of the American Chemical Society, 2003, vol. 125, # 26, p. 7792 - 7793
[5] Synthesis, 2011, # 6, p. 857 - 859
  • 30
  • [ 108-37-2 ]
  • [ 108-18-9 ]
  • [ 79-22-1 ]
  • [ 31603-49-3 ]
  • [ 685892-23-3 ]
Reference: [1] Organic Process Research and Development, 2005, vol. 9, # 6, p. 764 - 767
  • 31
  • [ 108-37-2 ]
  • [ 2312-23-4 ]
Reference: [1] Chinese Journal of Chemistry, 2018, vol. 36, # 11, p. 1003 - 1006
  • 32
  • [ 109-01-3 ]
  • [ 108-37-2 ]
  • [ 148546-99-0 ]
Reference: [1] Organic Letters, 2018, vol. 20, # 8, p. 2301 - 2305
  • 33
  • [ 108-37-2 ]
  • [ 95-92-1 ]
  • [ 62123-73-3 ]
Reference: [1] Chemical Communications, 2013, vol. 49, # 32, p. 3300 - 3302
[2] Organic Letters, 2016, vol. 18, # 9, p. 2122 - 2125
  • 34
  • [ 108-37-2 ]
  • [ 450412-28-9 ]
YieldReaction ConditionsOperation in experiment
91%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 3 h;
Stage #2: With iodine In tetrahydrofuran; hexane at -78 - 20℃; for 20 h;
To a solution of diisopropylamine (76 mL, 0.4 mol) in anhydrous THF (664 mL) and n-hexane (220 mL) was added 2.5 M n-BuLi (160 mL, 0.4 mol) dropwise at -78 0C over 1 h. The mixture was stirred for 1 h at -78 0C and a solution of 1-bromo- 3-chlorobenzene (76 g, 0.4 mol) in anhydrous THF (300 mL) was added dropwise at - 78 0C. After stirring for an additional 1 h at the same temperature, a solution of iodine (101 g, 0.4 mol) in anhydrous THF (400 mL) was added dropwise at -78 0C. The temperature was raised from -78 0C to rt during 2 h. After stirring for 18 h at rt, the mixture was concentrated in vacuo to give the crude product (120 g) which was distilled under reduced pressure to give l-bromo-3-fluoro-2-iodobenzene (115 g, 91percent). 1H NMR (400MHz, CDCl3): 7.12-7.18 (t, IH), 7.35-7.41 (dd, IH), 7.49-7.54 (dd, IH); MS (E/Z): 317 (M+H+)
91%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 1 h;
Stage #2: With iodine In tetrahydrofuran at -78 - 20℃; for 20 h;
To a solution of diisopropylamine (76 mL, 0.4 mol) in anhydrous THF (664 mL) and n-hexane (220 mL) was added 2.5 M n-BuLi (160 mL, 0.4 mol) dropwise at -78° C. over 1 h. The mixture was stirred for 1 h at -78° C. and a solution of 1-bromo-3-chlorobenzene (76 g, 0.4 mol) in anhydrous THF (300 mL) was added dropwise at -78° C. After stirring for an additional 1 h at the same temperature, a solution of iodine (101 g, 0.4 mol) in anhydrous THF (400 mL) was added dropwise at -78° C. The temperature was raised from -78° C. to rt during 2 h. After stirring for 18 h at rt, the mixture was concentrated in vacuo to give the crude product (120 g) which was distilled under reduced pressure to give 1-bromo-3-fluoro-2-iodobenzene (115 g, 91percent). 1H NMR (400 MHz, CDCl3) δ ppm 7.12-7.18 (t, 1H), 7.35-7.41 (dd, 1H), 7.49-7.54 (dd, 1H); MS (E/Z): 317 (M+H+)
91%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 1 h;
Stage #2: With iodine In tetrahydrofuran; hexane at -78 - 20℃; for 20 h;
b) 6-Bromo-2-chloro-3 '-methyl-biphenylStep 1. l-bromo-3-chloro-2-iodobenzene: To a solution of diisopropylamine (76 mL, 0.4 mol) in anhydrous THF (664 mL) and n-hexane (220 mL) was added 2.5 M n-BuLi (160 mL, 0.4 mol) dropwise at -78 0C over 1 h. The mixture was stirred for 1 h at -78 0C and a solution of l-bromo-3-chlorobenzene (76 g, 0.4 mol) in anhydrous THF (300 mL) was added dropwise at -78 0C. After stirring for an additional 1 h at the same temperature, a solution of iodine (101 g, 0.4 mol) in anhydrous THF (400 mL) was added dropwise at -78 0C. The temperature was raised from -78 0C to rt during 2 h. After stirring for 18 h at rt, the mixture was <n="88"/>concentrated in vacuo to give the crude product (120 g) which was distilled under reduced pressure to give l-bromo-3-fluoro-2-iodobenzene (115 g, 91percent). 1H NMR (400MHz, CDCl3): 7.12-7.18 (t, IH), 7.35-7.41 (dd, IH), 7.49-7.54 (dd, IH); MS (E/Z): 317 (M+H+)
91%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 2 h;
Stage #2: at -78℃; for 1 h;
Stage #3: With iodine In tetrahydrofuran; hexane at -78 - 20℃; for 20 h;
To a solution of diisopropylamine (76 mL, 0.4 mol) in anhydrous THF (664 niL) and n-hexane (220 mL) was added 2.5 M "-BuLi (160 mL, 0.4 mol) dropwise* at -78 0C over 1 h. The mixture was stirred for 1 h at -78 0C and a solution of 1 - bromo-3-chlorobenzene (76 g, 0.4 mol) in anhydrous THF (300 mL) was added dropwise at -78 0C. After stirring for an additional 1 h at the same temperature, a solution of iodine (101 g, 0.4 mol) in anhydrous THF (400 mL) was added dropwise at -78 0C. The temperature was raised from -78 0C to room temperature during 2 h. After stirring for 18 h at rt, the mixture was concentrated in vacuo to give the crude product (120 g) which was distilled under reduced pressure to give l -bromo-3- fluoro-2-iodobenzene (1 15 g, 91percent). 1H NMR (400MHz, CDCl3): 7.12-7.18 (t, IH), 7.35-7.41 (dd, IH), 7.49-7.54 (dd, IH); MS (E/Z): 317 (M+H+)
91%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane, n- at -78℃; for 3 h;
Stage #2: With iodine In tetrahydrofuran; hexane, n- at -78 - 20℃; for 20 h;
To a solution of diisopropylamine (76 niL, 0.4 mol) in anhydrous THF (664 rnL) and n-hexane (220 rnL) was added 2.5 M n-BuLi (160 rnL, 0.4 mol) dropwise at -78 0C over 1 h. The mixture was stirred for 1 h at -78 0C and a solution of 1-bromo- 3-chlorobenzene (76 g, 0.4 mol) in anhydrous THF (300 mL) was added dropwise at - 78 0C. After stirring for an additional 1 h at the same temperature, a solution of iodine (101 g, 0.4 mol) in anhydrous THF (400 mL) was added dropwise at -78 0C. The temperature was raised from -78 0C to rt during 2 h. After stirring for 18 h at rt, the mixture was concentrated in vacuo to give the crude product (120 g) which was distilled under reduced pressure to give l-bromo-3-fluoro-2-iodobenzene (115 g, 91percent). 1H NMR (400MHz, CDCl3): 7.12-7.18 (t, IH), 7.35-7.41 (dd, IH), 7.49-7.54 (dd, IH); MS (E/Z): 317 (M+H+)

Reference: [1] Patent: WO2008/124575, 2008, A1, . Location in patent: Page/Page column 103
[2] Patent: US2010/317697, 2010, A1, . Location in patent: Page/Page column 47
[3] Patent: WO2008/124582, 2008, A1, . Location in patent: Page/Page column 86-87
[4] Patent: WO2007/117560, 2007, A2, . Location in patent: Page/Page column 169
[5] Patent: WO2008/124577, 2008, A1, . Location in patent: Page/Page column 69
[6] Chemistry - A European Journal, 2012, vol. 18, # 45, p. 14232 - 14236
[7] Angewandte Chemie - International Edition, 2002, vol. 41, # 22, p. 4272 - 4274
[8] Advanced Synthesis and Catalysis, 2007, vol. 349, # 17-18, p. 2705 - 2713
[9] Journal of the American Chemical Society, 2002, vol. 124, # 29, p. 8514 - 8515
[10] Journal of the American Chemical Society, 2008, vol. 130, # 2, p. 472 - 480
[11] Organic Letters, 2004, vol. 6, # 10, p. 1589 - 1592
[12] Tetrahedron Letters, 2009, vol. 50, # 17, p. 1920 - 1923
  • 35
  • [ 108-37-2 ]
  • [ 159724-40-0 ]
Reference: [1] Organic Letters, 2018, vol. 20, # 8, p. 2301 - 2305
  • 36
  • [ 108-37-2 ]
  • [ 173676-59-0 ]
Reference: [1] Patent: CN106518636, 2017, A,
  • 37
  • [ 108-37-2 ]
  • [ 870119-58-7 ]
Reference: [1] Patent: KR2015/84657, 2015, A,
[2] Patent: KR2015/24669, 2015, A,
  • 38
  • [ 108-37-2 ]
  • [ 1115023-84-1 ]
Reference: [1] Patent: KR2017/124412, 2017, A,
  • 39
  • [ 108-37-2 ]
  • [ 5122-95-2 ]
  • [ 1115023-84-1 ]
Reference: [1] Patent: KR2015/84657, 2015, A,
  • 40
  • [ 108-37-2 ]
  • [ 1048916-71-7 ]
Reference: [1] Journal of the American Chemical Society, 2012, vol. 134, # 41, p. 17023 - 17026,4
[2] Journal of the American Chemical Society, 2012, vol. 134, # 41, p. 17023 - 17026
[3] Journal of the American Chemical Society, 2012, vol. 134, # 49, p. 20208 - 20208
[4] Angewandte Chemie - International Edition, 2015, vol. 54, # 49, p. 14748 - 14752[5] Angew. Chem., 2015, vol. 127, # 49, p. 14961 - 14965,5
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