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Chemical Structure| 42860-10-6 Chemical Structure| 42860-10-6

Structure of 42860-10-6

Chemical Structure| 42860-10-6

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Product Details of [ 42860-10-6 ]

CAS No. :42860-10-6
Formula : C7H4BrClO2
M.W : 235.46
SMILES Code : BrC1=C(C=CC(=C1)C(=O)O)Cl
MDL No. :MFCD00079706
Boiling Point : No data available
InChI Key :NLEPZGNUPNMRGF-UHFFFAOYSA-N
Pubchem ID :2735544

Safety of [ 42860-10-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 42860-10-6 ] 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 2.0
Num. H-bond donors 1.0
Molar Refractivity 46.11
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

37.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.66
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

3.52
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.8
Log Po/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.

2.94
Log Po/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

2.54
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.69

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.86
Solubility 0.0329 mg/ml ; 0.00014 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.

-3.99
Solubility 0.0243 mg/ml ; 0.000103 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

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

-3.25
Solubility 0.134 mg/ml ; 0.000568 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

No
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.

-5.24 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.

0.56

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

0.0 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<2.0
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)

1.41

Application In Synthesis of [ 42860-10-6 ]

* 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 [ 42860-10-6 ]

[ 42860-10-6 ] Synthesis Path-Downstream   1~37

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YieldReaction ConditionsOperation in experiment
With thionyl chloride;N,N-dimethyl-formamide; at 80℃; for 2h; Example 4; (Method C) <n="51"/>Example 4aSynthesis of 3-Bromo-4-chlorobenzamideTo a mixture of S-bromo^-chlorobenzoic acid (5.07 g, 22 mmol, Alfa Aesar) and thionyl chloride (15 ml, 206 mmol) was added 1 drop of DMF and the reaction was heated at 80 0C. After 2 h the excess SOCl2 was removed in vacuo and the residue was azeotroped with toluene (2x). The residue was dissolved in 40 mL OfCH2Cl2 and cooled to 0 0C. Ammonia was bubbled into the reaction for 30 min. The mixture was diluted with 200 mL Of CH2Cl2 and washed with saturated NaHCO3. The aqueous layer was extracted with CH2Cl2 (3x) and the combined organic layers were washed with H2O and dried over Na2SO4 to give 3.81 g (75percent) of a white amorphous solid. MS- m/z: 233.9, 235.9 [M+l].
With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 20 - 40℃; for 1h; Step 1. To a solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> 71 (5.30 g, 23 mmol) in DCM (10 mL) at room temperature was added DMF (5 drops) and oxalyl dichloride (3.0 mL, 34 mmol). The reaction mixture was heated to 40° C. for 1 h. The solvent and excess oxalyl chloride were removed under a stream of nitrogen followed by high vacuum. The acid chloride was dissolved in DCM (100 mL), cooled to 0° C., and then pyridine (2.8 mL, 34 mmol) was added followed by (R)-1-phenylethanamine (3.8 mL, 30 mmol). The reaction mixture was stirred at 0° C. for 1 h and concentrated under reduced pressure. The crude amide was dissolved in EtOAc, washed with 1 M HCl (2*), brine (1*), dried over MgSO4, filtered, and concentrated to give (R)-3-bromo-4-chloro-N-(1-phenylethyl)benzamide 72 (8.15 g, 71percent yield) as a white solid which was used without further purification. Mass spectrum: calculated for C15H13BrClNO 337.0; found 338.0 (M++1).
With thionyl chloride; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; for 2h; Step 1. A solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> 104 (2.354 g, 10.0 mmol) in 30 mL of CH2Cl2 was chilled to 0° C. in an ice bath. To this solution was added a solution of thionyl chloride (2.2 mL, 30 mmol) in CH2Cl2 and then a few drops of DMF. The reaction was warmed to room temperature and stirred under N2 for 2 h. The reaction mixture was concentrated in vacuo. The crude acid chloride was re-dissolved in CH2Cl2 and it was chilled to 0° C. Triethylamine (2.8 mL, 20 mmol) was slowly added to the reaction via syringe. The reaction was warmed to room temperature and stirred for 2 h under N2. The reaction mixture was concentrated and then diluted with EtOAc. The solution was extracted with saturated NaHCO3, water, and brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by ISCO flash chromatography using a 5percent to 60percent gradient of EtOAc in hexanes as the eluant. The desired fractions were combined and concentrated to give 3-bromo-4-chloro-N-methoxy-N-methylbenzamide 105 (2.43 g, 87percent yield) as a colorless oil.
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; Example 77 3-Bromo-4-chlorobenzamide 3-Bromo-4-chlorobenzoic acid (2.35 g, 10 mmol) was suspended in CH2Cl2 (50 mL) and stirred under argon at room temperature. Oxalyl chloride (2.53 g, 20 mmol) was added followed by DMF (10 muL). Gas evolution began, and the mixture was stirred until gas evolution ceased. The solvents were pumped off and toluene was added and stripped off to remove excess oxalyl chloride. The residue was taken up in EtOAc and added to concentrated ammonium hydroxide (10 mL). This was stirred for 30 min. The phases were separated and the organic washed 1* with brine dried over anhydrous Na2SO4, filtered, and evaporated. The residue was crystallized from EtOAc/hexane to give the title compound as a white crystalline solid. LC-MS m/z 233.7 (M+H)+, 1.54 min (ret time); mp 146-147° C.; analytical HPLC shows 100percent purity, (ret time: 11.835 min).
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃;Inert atmosphere; Example 94 3-Bromo-4-chlorobenzamide 3-Bromo-4-chlorobenzoic acid (2.35 g, 10 mmol) was suspended in CH2Cl2 (50 mL) and stirred under argon at room temperature. Oxalyl chloride (2.53 g, 20 mmol) was added followed by DMF (10 muL). Gas evolution began, and the mixture was stirred until gas evolution ceased. The solvents were pumped off and toluene was added and stripped off to remove excess oxalyl chloride. The residue was taken up in EtOAc and added to concentrated ammonium hydroxide (10 mL). This was stirred for thirty min. The phases were separated and the organic washed 1* with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was crystallized from EtOAc/hexane to give the title compound as a white crystalline solid. LC-MS m/z 233.7 (M+H)+, 1.54 min (ret time); mp 146-147° C.; analytical HPLC shows 100percent purity, (ret time 11.835 min).
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃;Inert atmosphere; Example 77 3-Bromo-4-chlorobenzamide3-Bromo-4-chlorobenzoic acid (2.35 g, 10 mmol) was suspended in CH2Cl2 (SO mL) and stirred under argon at room temperature. Oxalyl chloride (2.53 g, 20 mmol) was added followed by DMF (10 muL). Gas evolution began, and the mixture was stirred until gas evolution ceased. The solvents were pumped off and toluene was added and stripped off to remove excess oxalyl chloride. The residue was taken up in EtOAc and added to concentrated ammonium hydroxide (10 mL). This was stirred for 30 min. The phases were separated and the organic washed IX with brine dried over anhydrous Na2SO4, filtered, and evaporated. The residue was crystallized from EtOAc/hexane to give the title compound as a white crystalline solid. LC-MS m/z 233.7 (M+H)+, 1.54 min (ret time); mp 146-147 0C; analytical HPLC shows 100percent purity, (ret time: 11.835 min).
With thionyl chloride; sodium chloride; In ethyl acetate; for 5h;Reflux; Inert atmosphere; To a stirred suspension of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (0.5 g) in EtOAc (10 mL) NaCl was added followed by the addition of 0.77 mL of thionyl chloride. This heterogeneous reaction mixture was then refluxed. After 5 hours, the reaction was cooled to room temperature and the volatiles were removed under reduced pressure. Excess solvent was removed and the residue was taken up in THF (10 mL) and cooled in an ice bath. Solid sodium cyanamide (0.272 g) was added to this stirred solution portionwise and the reaction was allowed to stir for twelve hours. Then THF was removed under reduced pressure and 15 mL of water was added to the residue. The solid was filtered off and the filtrate was acidified with IN aq. HC1. The precipitated white solid was isolated, filtered, and dried. Compound S3 was carried forward without additional purification.
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; for 1h; To <strong>[42860-10-6]3-bromo-4-chloro-benzoic acid</strong> (9.4 g, 40 mmol ) in dry DCM (100 mL), was added DMF (0.5 ml.) followed by addition of oxalyl chloride (22.5 ml_, 55 mmol, 2M in DCM ) slowly. The mixture was stirred for 1 hr, then concentrated to yield 3-bromo-4-chloro-benzoyl chloride as an off-white solid.

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  • [ 86265-88-5 ]
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  • [ 289039-24-3 ]
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  • [ 108-95-2 ]
  • 3-bromo-4-chloro-benzoic acid phenyl ester [ No CAS ]
  • 7
  • [ 64-17-5 ]
  • [ 42860-10-6 ]
  • [ 76008-75-8 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In 1,4-dioxane; for 24h;Heating / reflux; Example 9A. 3-Bromo-4-chlorobenzoic acid ethyl ester.To a solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (5.0 g, 21 mmol) in 150 mL absolute ethanol was added 15 mL of 4N HCl/dioxane. The mixture was heated to reflux for 24 hours then cooled to ambient temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and H2O, and the separated organic phase was washed sequentially with saturated NaHCpsi3 solution, brine, dried (Na2SO-O, filtered and concentrated under reduced pressure to provide the title compound. 1H NMR (DMSO-ddelta) delta 8.22 (d, IH), 7.94 (dd, IH), 7.80 (d, IH), 4.33 (q, 2H), 1.33 (t, 3H); MS (DCI4) m/z 263 (M+H)+.
  • 8
  • [ 54826-14-1 ]
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  • [ 7790-94-5 ]
  • [ 7726-95-6 ]
  • [ 74-11-3 ]
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  • 10
  • [ 74-11-3 ]
  • sodium bromide [ No CAS ]
  • sulfur [ No CAS ]
  • [ 42860-10-6 ]
  • 11
  • 1-<4-chloro-3-bromo-phenyl>-ethanone-(1) [ No CAS ]
  • [ 42860-10-6 ]
  • 12
  • [ 289039-24-3 ]
  • [ 7697-37-2 ]
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  • 13
  • [ 2840-28-0 ]
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  • [ 42860-10-6 ]
  • [ 938163-32-7 ]
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  • [ 42860-10-6 ]
  • [ 938163-38-3 ]
  • 16
  • [ 42860-10-6 ]
  • [ 938163-43-0 ]
  • 17
  • [ 42860-10-6 ]
  • C10H7BrClN3O [ No CAS ]
  • 18
  • [ 42860-10-6 ]
  • 2-amino-4-(3-bromo-4-chlorophenyl)thiazole-5-carboxamide hydrobromide [ No CAS ]
  • 19
  • [ 42860-10-6 ]
  • C10H6BrClN2OS [ No CAS ]
  • 20
  • [ 42860-10-6 ]
  • [ 913067-93-3 ]
  • 21
  • [ 42860-10-6 ]
  • 3-(2-amino-6-quinazolinyl)-4-chloro-N-(3-(trifluoromethyl)phenyl)benzamide [ No CAS ]
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  • [ 42860-10-6 ]
  • [ 782-03-6 ]
  • 23
  • [ 42860-10-6 ]
  • [ 834895-52-2 ]
  • 24
  • [ 42860-10-6 ]
  • [ 834895-57-7 ]
  • 25
  • [ 42860-10-6 ]
  • 1-(3-bromo-4-pyrrolidin-1-yl-phenyl)-1-phenyl-3-trimethylsilanyl-prop-2-yn-1-ol [ No CAS ]
  • 26
  • [ 42860-10-6 ]
  • [ 834895-43-1 ]
  • 27
  • [ 42860-10-6 ]
  • 1-[(E)-3-(3-Bromo-4-pyrrolidin-1-yl-phenyl)-3-phenyl-prop-2-en-(Z)-ylidene]-1H-naphthalen-2-one [ No CAS ]
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  • [ 16588-34-4 ]
  • [ 42860-10-6 ]
  • 29
  • [ 622-98-0 ]
  • [ 42860-10-6 ]
  • 30
  • [ 100-41-4 ]
  • [ 42860-10-6 ]
  • 31
  • [ 106-43-4 ]
  • [ 42860-10-6 ]
  • 32
  • [ 42860-10-6 ]
  • 3-bromo-4-chloro-benzoic acid menthyl ester [ No CAS ]
  • 33
  • [ 89-62-3 ]
  • [ 42860-10-6 ]
  • 34
  • [ 42860-10-6 ]
  • 3-Brom-4-chlor-4'-methyl-benzophenon [ No CAS ]
  • 35
  • [ 694-80-4 ]
  • [ 42860-10-6 ]
  • 36
  • [ 42860-10-6 ]
  • [ 329218-12-4 ]
YieldReaction ConditionsOperation in experiment
100% With borane-THF; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; A. (3-Bromo-4-chloro-phenyl)-methanolTo a mixture of <strong>[42860-10-6]3-bromo-4-chloro-benzoic acid</strong> (10.0 g, 42.5 mmol) in THF (50 mL) under nitrogen at 0 °C is added 1 .0 M solution of borane.THF (55.3 mL, 55.3 mmol). After stirring at ambient temperature overnight the reaction is poured into a mixture of NaHCO3/H2O/ice and extracted with EtOAc. The organic layer is washed with saturated aqueous NaCI, dried over MgSO4, filtered and concentrated in vacuo to provide the desired product (9.4 g, 100percent) as a clear, colorless oil.1 H NMR (300 MHz, CDCI3) delta 7.61 (s, 1 H), 7.41 (d, J = 5.1 Hz, 1 H), 7.21 (d, J = 5.1 Hz, 1 H), 4.63 (s, 2H), 2.12 (br s, 1 H).
92% With dimethylsulfide borane complex; In tetrahydrofuran; at 20℃; General procedure: <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (34.2 g, 145.25 mmol) was dissolved in THF (250 ml)and cooled to 0 °C, to this was added borane-methyl sulfide complex (153 ml,305.02 mmol) and the reaction was warmed to room temperature and stirred overthe weekend. The reaction was very carefully quenched with saturated Na2CO3 (100mL), extracted with EtOAc (3 x 100 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford a colourless liquid. The crude product was purifiedby distillation at 0.2 mBar, collecting fractions that distilled at 100 °C to afford (3-bromo-4-chlorophenyl)methanol (29.5 g, 92 percent) as a colourless liquid.
90% With dimethylsulfide borane complex; In tetrahydrofuran; at 0 - 80℃; for 1.5h;Reflux; Example 6, Step 1To a solution of 3-bromo-4-benzoic acid 6-1 (4.0 g, 17.0 mmol) in anhydrous TI{F (18 mL) was slowly added BH3.DMS (1.6 g, 20.4 mmol) at 0°C then the reaction was refluxed at 80°C for 90 mm. The mixture was cooled and concentrated in vacuo, diluted with water and extracted with DCM. The organic layer was washed with saturated aqueous sodium bicarbonate solution then brine, dried over Na2SO4 and concentrated in vacuo. The residue waspurified by chromatography over silica gel (eluting with hexanes/EtOAc 100:0 to 0:100) to afford 3.4 g (90percent) of intermediate 6-2.
Example 12 4-Aminomethyl-cyclohexanecarboxylic acid {1-[3-(3-amino-1H-indazol-6-yl)-4-chloro-phenyl]-2-phenyl-ethyl}-amide 12A. 3-Bromo-4-chloro-benzaldehyde: To a cooled (0° C.), clear, colorless solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (1.0 g, 4.25 mmol) in THF (43 mL) was added dropwise a 1.0 M borane-THF complex (12.7 mL, 12.7 mmol). After 15 min, the reaction was warmed to rt and then to reflux. After 2 h, the reaction was cooled to rt, then to 0° C., and then quenched with MeOH (10 mL). The reaction was warmed to rt and after 15 min., the reaction was concentrated. The residue was dissolved in EtOAc and washed with 1.0 N HCl, sat. NaHCO3, brine, dried over Na2SO4, filtered and concentrated to give a clear, colorless liquid. The liquid was dissolved in CH2Cl2 (17 mL) and cooled to 0° C. Next Dess-Martin periodinane (2.16 g, 5.10 mmol) was added. The resulting cloudy pale orange suspension was stirred for 30 min. and then diluted with Et2O (50 mL). The reaction was filtered through a plug of silica gel and the filtrate was concentrated to give an off-white solid. Column chromatography on silica gel (gradient elution 0-25percent EtOAc in Hex) gave 0.815 g (87percent) of the aldehyde as a white solid. 1H NMR (400 MHz, CDCl3) delta: 9.94 (s, 1H), 8.13 (d, J=1.8 Hz, 1H), 7.77 (dd, J=8.1, 2.0 Hz, 1H), 7.63 (d, J=7.9 Hz, 1H).
With borane; In tetrahydrofuran; at 65℃; for 12h; A solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (3.53 g, 15 mmol) was dissolved in anhydrous THF (20 [ML)] and cooled to 0 C prior to addition of borane [(1M] soln in [THF,] 20 mL, 20 mmol). The solution was then heated at 65 C for 12 hours then cooled to 0 C and methanol was added dropwise to quench excess borane. The solvent was evaporated under reduced pressure, the residue was redissolved in ethyl acetate and washed with saturated NH4Cl then brine, dried over sodium sulphate. The solvent was removed in vacuo to afford 3.23 g of title compound. [ <P>C7H6BRC10] Mass (calculated): [221], [MH NOT] found. NMR (400 MHz, CDC13) : 4.6 (2H, s, CH20H); 7.15 [(1H,] dd, [J=] 1 and 8 Hz, aryl- H); 7.35 [(1H,] d, [J =] 8 Hz, aryl-H); 7.55 [(1H,] d, [J = 1 HZ,] aryl-H).
Step 1:199.0 g (0.845 mol) of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> were dissolved in 2.5 litres of THF, the mixture was cooled to -10° C. and 1.69 litres (1.69 mol) of a 1 M solution of borane in THF were added at this temperature. The reaction mixture was warmed to RT overnight, and saturated aqueous ammonium chloride solution was then added. After the addition of water, the mixture was extracted twice with ethyl acetate and the combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. This gave, as a crude product, 206 g of (3-bromo-4-chlorophenyl)methanol which were used in the subsequent step without further purification.
Example 28A2-Bromo-4-(bromomethyl)-1-chlorobenzene Step 1:199.0 g (0.845 mol) of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> were dissolved in 2.5 litres of THF, the mixture was cooled to -10° C. and 1.69 litres (1.69 mol) of a 1 M solution of borane in THF were added at this temperature. The reaction mixture was warmed to RT overnight, and saturated aqueous ammonium chloride solution was then added. After addition of water, the mixture was extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. This gave 206 g of (3-bromo-4-chlorophenyl)methanol as a crude product which was reacted without further purification.
With borane-THF; In tetrahydrofuran; at -10 - 20℃; Step 1: [0430] 199.0 g (0.845 mol) of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> were dissolved in 2.5 litres of THF, the solution was cooled to ?10° C. and 1.69 litres (1.69 mol) of a 1 M solution of borane in THF were added at this temperature. The reaction mixture was warmed to RT overnight, and saturated aqueous ammonium chloride solution was then added. After addition of water, the mixture was extracted twice with ethyl acetate, and the combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. This gave, as a crude product, 206 g of (3-bromo-4-chlorophenyl)methanol which were used without further purification for the next step.

  • 37
  • [ 42860-10-6 ]
  • [ 75-03-6 ]
  • [ 76008-75-8 ]
YieldReaction ConditionsOperation in experiment
97% With caesium carbonate; In hexane; ethyl acetate; acetonitrile; a. Ethyl <strong>[42860-10-6]3-bromo-4-chlorobenzoate</strong>. To a solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (3.00 g, 12.74 mmol) and cesium carbonate (6.23 g, 19.11 mmol) in acetonitrile (70 mL) was added iodoethane (5.1 mL, 63.7 mmol). The reaction mixture was heated at reflux overnight. After cooling to room temperature, the solution was extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. Choromatography on silica gel (biotage, 5percent EtOAc in hexane) afforded 3.5 g of ethyl <strong>[42860-10-6]3-bromo-4-chlorobenzoate</strong> (97percent). 1H NMR (300 MHz; CDCl3) delta1.40 (t, 3H); 4.37 (q, 2H); 7.52 (d, J=8.1 Hz, 1H); 7.91 (dd, J1=8.4 Hz, J2=1.8 Hz, 1H); 8.28 (d, J=1.8 Hz, 1H).
97% With caesium carbonate; In hexane; ethyl acetate; acetonitrile; a. Ethyl <strong>[42860-10-6]3-bromo-4-chlorobenzoate</strong> To a solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (3.00 g, 12.74 mmol) and cesium carbonate (6.23 g, 19.11 mmol) in acetonitrile (70 mL) was added iodoethane (5.1 mL, 63.7 mmol). The reaction mixture was heated at reflux overnight. After cooling to room temperature, the solution was extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. Choromatography on silica gel (biotage, 5percent EtOAc in hexane) afforded 3.5 g of ethyl <strong>[42860-10-6]3-bromo-4-chlorobenzoate</strong> (97percent). 1H NMR (300 MHz; CDCl3) 1.40 (t, 3H); 4.37 (q, 2H); 7.52 (d, J=8.1 Hz, 1H); 7.91 (dd, J1=8.4 Hz, J2=1.8 Hz, 1H); 8.28 (d, J=1.8 Hz, 1H).
 

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