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Chemical Structure| 539-74-2 Chemical Structure| 539-74-2

Structure of Ethyl 3-bromopropionate
CAS No.: 539-74-2

Chemical Structure| 539-74-2

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Product Details of [ 539-74-2 ]

CAS No. :539-74-2
Formula : C5H9BrO2
M.W : 181.03
SMILES Code : CCOC(=O)CCBr
MDL No. :MFCD00000251
InChI Key :FQTIYMRSUOADDK-UHFFFAOYSA-N
Pubchem ID :68320

Safety of [ 539-74-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H315-H319-H335
Precautionary Statements:P305+P351+P338

Computational Chemistry of [ 539-74-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 4
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 35.3
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.09
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

1.18
Log Po/w (WLOGP)?

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

1.33
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.

1.45
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

1.34
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.48

Water Solubility

Log S (ESOL):?

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

-1.44
Solubility 6.55 mg/ml ; 0.0362 mol/l
Class?

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

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.33
Solubility 8.51 mg/ml ; 0.047 mol/l
Class?

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

Very 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

-2.02
Solubility 1.72 mg/ml ; 0.00951 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.

-6.57 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

1.0
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

1.0 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)

1.94

Application In Synthesis of [ 539-74-2 ]

* 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.

  • Downstream synthetic route of [ 539-74-2 ]

[ 539-74-2 ] Synthesis Path-Downstream   1~23

  • 2
  • [ 539-74-2 ]
  • [ 75-16-1 ]
  • [ 35979-69-2 ]
YieldReaction ConditionsOperation in experiment
75.1% In tetrahydrofuran; at 0℃; Intermediate 45 4-bromo-2-methylbutan-2-ol To a solution of methyl 3-bromopropanoate (0.2 g, 1.2 mmol,) in THF (5 mL) was added methyl magnesium bromide (2.4 mL, 2.4 mmol) at 0 C. The mixture was stirred at this temperature until the substrate was consumed based on tic [petroleum ether/ethyl acetate (3: 1); product Rf 0.3]. The reaction was quenched with ammonium chloride (2 mL) at 0 C. The mixture was partitioned between ethyl acetate and water. The combined organic layer was dried over sodium sulfate, filtered and concentrated, to give a crude product which was purified by a column chromatography eluting with petroleum ether/ ethyl acetate (3: 1 ) to give 4-bromo-2- methylbutan-2-ol (0.15 g, 75.1 % yield) as a yellow oil.
In diethyl ether; at 0℃; a) 4-Bromo-2-methylbutan-2-olTo a cooled solution of ethyl 3-bromopropanoate (0.5 g, 2.8 mmol) in diethyl ether (50 ml) at 0 C was added methyl magnesium bromide (0.98 g, 8.3 mmol, 3 eq.) dropwise over 5 min and the mixture was allowed to stir until TLC showed complete absence of the starting material. The mixture was quenched and extracted as in Inter- mediate Example 5(c). The solvent was distilled off to give the crude product (0.4 g).
In diethyl ether; at 0℃; for 0.0833333h; To a cooled solution of ethyl 3-bromopropanoate (0.5 g, 2.8 mmol) in diethyl ether (50 ml) at 0 C. was added methyl magnesium bromide (0.98 g, 8.3 mmol, 3 eq.) dropwise over 5 min and the mixture was allowed to stir until TLC showed complete absence of the starting material. The mixture was quenched and extracted as in Intermediate Example 5(c). The solvent was distilled off to give the crude product (0.4 g).
In diethyl ether; at -20 - 20℃; for 2h; Methyl magnesium bromide (11.04 mL, 33.14 mmol) was added drop wise over 10 min to a well-stirred mixture of ethyl 3-bromopropanoate (compound 24; 2.0 g, 11.04 mmol) in diethyl ether (25 mL) at -20 C. The reaction mixture was stirred at rt for over 2 h. On completion the reaction mixture was poured into aq. NH4Cl (25 mL) and extracted with EtOAc (2*25 mL). The combined organic layers were washed with H2O (100 mL) and brine (100 mL), separated and then dried over anhydrous Na2SO4. Evaporated under reduced pressure yielded 2.1 g of crude compound 25 which was used directly in the next step without any further purification.

  • 3
  • [ 539-74-2 ]
  • [ 6414-69-3 ]
YieldReaction ConditionsOperation in experiment
With sodium iodide; In acetone; for 5h;Reflux; 57aTo a solution of ethyl 3-bromopropanoate (120 g, 663 mmol) in acetone (500 mE) was added Nal (150 g, 1.00 mol). The resulting solution was heated at reflux for 5 h and allowed to cool to rt. Et20 (500 mE) was added. The solids formed were removed by filtration. The filtrate was concentrated in vacuo. The resulting residue was treated with Et20 (150 mE) and filtered. The filtrate was washed with saturated NaHCO3 solution (2x50 mE). The organic layer was dried over Na2504, filtered and concentrated under reduced pressure to obtain compound 57a as a yellow oil. Mass Spectrum (GCMS, ESI pos.): Calcd. for C5H9102: 228.0 (M). Found:228.0.
  • 4
  • [ 539-74-2 ]
  • [ 49701-79-3 ]
  • [ 98300-24-4 ]
YieldReaction ConditionsOperation in experiment
15% With sodium hydrogencarbonate; triethylamine; In hexane; ethyl acetate; EXAMPLE 1 2'-(N-2-Carbethoxyethylamino)-3',4'-dimethoxyacetophenone Triethylamine (19.4 g, 192 mM) was added to a mixture of <strong>[49701-79-3]2'-amino-3',4'-dimethoxyacetophenone</strong> (25 g, 128 mM) and ethyl 3-bromopropionate (139 g, 770 mM), in a 250 mL flask (equipped with a large stirring bar, reflux condenser and nitrogen inlet). The pale solid which formed was stirred at 135 C. for 5 hours. The brown homogeneous oil which formed was then cooled to 10 C. and 200 mL of 2% NaHCO3 was added. The solution was then extracted with CHCl3 (3*100 mL), the organic layer washed with H2 O (100 mL) and dried over MgSO4. Following filtration, the CHCl3 and most of the bromopropionate were removed under reduced pressure. The oily residue was charged onto a 10*75 cm, SilicAR CC-7 column (800 g, hexane packed) and eluted with 5 to 20% ethylacetate/hexane, collecting 1 L fractions. Evaporation of fractions 7-9 gave purified 2'-(N-2-carbethoxyethylamino)-3',4'-dimethoxyacetophenone as a yellow oil (5.86 g, 15%); UV (EtOH) nm: 244 (epsilon29110), 284 (epsilon11480); MS (Probe) 295 (M+).
15% With sodium hydrogencarbonate; triethylamine; In hexane; ethyl acetate; EXAMPLE 1 2'-(N-2-Carbethoxyethylamino)-3',4'-dimethoxyacetophenone Triethylamine (19.4 g, 192 mM) was added to a mixture of <strong>[49701-79-3]2'-amino-3',4'-dimethoxyacetophenone</strong> (25 g, 128 mM) and ethyl 3-bromopropionate (139 g, 770 mM), in a 250 mL flask (equipped with a large stirring bar, reflux condenser and nitrogen inlet). The pale solid which formed was stirred at 135 C. for 5 hours. The brown homogeneous oil which formed was then cooled to 10 C. and 200 mL of 2% NaHCO3 was added. The solution was then extracted with CHCl3 (3*100 mL), the organic layer washed with H2 O (100 mL) and dried over MgSO4. Following filtration, the CHCl3 and most of the bromopropionate were removed under reduced pressure. The oily residue was charged onto a 10*75 cm, SilicAR CC-7 column (800 g, hexane packed) and eluted with 5 to 20% ethyl acetate/hexane, collecting 1 L fractions. Evaporation of fractions 7-9 gave purified 2'-(N-2-carbethoxyethylamino)-3',4'-dimethoxyacetophenone as a yellow oil (5.86 g, 15%); UV (EtOH) nm: 244 (epsilon29110), 284 (epsilon11480); MS (Probe) 295 (M+).
  • 5
  • [ 539-74-2 ]
  • [ 18593-44-7 ]
  • [ 108311-84-8 ]
  • 6
  • [ 539-74-2 ]
  • [ 56741-95-8 ]
  • [ 154379-13-2 ]
  • 7
  • [ 539-74-2 ]
  • [ 172168-01-3 ]
  • [ 1026968-77-3 ]
  • 8
  • [ 539-74-2 ]
  • N-<β-ethoxycarbonyl-ethyl>-benzylamine [ No CAS ]
  • [ 6938-07-4 ]
  • 10
  • [ 123-00-2 ]
  • [ 87543-80-4 ]
  • [ 539-74-2 ]
  • [ 774-07-2 ]
  • 2-[1-(2-ethoxycarbonyl-ethyl)-7-(3-morpholin-4-yl-propylamino)-2,4-dioxo-1,4-dihydro-2<i>H</i>-pyrimido[4,5-<i>d</i>]pyrimidin-3-yl]-3-phenyl-propionic acid ethyl ester [ No CAS ]
  • 11
  • [ 36822-11-4 ]
  • [ 539-74-2 ]
  • 3-(6-oxo-4-phenyl-1,6-dihydro-pyrimidin-2-ylsulfanyl)-propionic acid ethyl ester [ No CAS ]
  • 12
  • [ 539-74-2 ]
  • [ 100-46-9 ]
  • [ 23583-21-3 ]
  • [ 6938-07-4 ]
  • 13
  • ethyl acetate n-hexane [ No CAS ]
  • [ 539-74-2 ]
  • [ 35979-69-2 ]
YieldReaction ConditionsOperation in experiment
2.57 g (45%) With hydrogenchloride; methylmagnesium bromide; In tetrahydrofuran; EXAMPLE 22 Preparation of 4-bromo-2-methyl-2-butanol To a solution of 6.25 g (34.5 mmol) of ethyl 3-bromopropionate in 28 ml of dry tetrahydrofuran at -20 C. was added dropwise 28.8 ml (80.6 mmol) of 2.8M methylmagnesium bromide in ether. The mixture was stirred at room temperature for 2 hours and 50 minutes then quenched by addition of 15 ml of saturated aqueous ammonium chloride. After addition of 42 ml of 1N aqueous HCl, the organic phase was separated and the aqueous phase extracted with ether. The combined organic extracts were washed with saturated brine, dried (Na2 SO4) and evaporated to dryness. The residue was chromatographed on silica gel (40-63μ) using 30% ethyl acetate-hexane to give 2.57 g (45%) of 4-bromo-2-methyl-2-butanol as an oil: IR (CHCl3) 3605 cm-1; 1 H NMR (CDCl3) δ1.27 (s, 6 H), 1.33 (s, 1 H), 2.11 (m, 2 H), 3.51 (m, 2 H); MS m/e 151 (M+ --CH3).
  • 14
  • [ 539-74-2 ]
  • [ 35979-69-2 ]
YieldReaction ConditionsOperation in experiment
With methylmagnesium bromide; In diethyl ether; 4-Bromo-2-methylbutan-2-ol Methylmagnesium bromide (3M in diethyl ether, 46 ml) was added to a solution of ethyl 3-bromopropionate (10 g) in diethyl ether (100 ml) at room temperature under argon. During this, the mixture was kept at above 20 C. and below 35 C. After 2 hours, the mixture was poured into a saturated ammonium chloride solution. This was followed by extraction with diethyl ether, drying with sodium sulfate, filtration and concentration. This resulted in the desired product.
  • 15
  • [ 539-74-2 ]
  • [ 56404-21-8 ]
  • [ 1030025-85-4 ]
YieldReaction ConditionsOperation in experiment
This compound was synthesized using the procedure described in example 2, step B, from 5-iodo-l,3-dimethyl-2-nitrobenzene (see example 2) and ethyl 3-bromopropanoate
  • 16
  • [ 773-76-2 ]
  • [ 539-74-2 ]
  • [ 1333378-70-3 ]
  • 17
  • [ 539-74-2 ]
  • [ 68838-94-8 ]
  • [ 1374963-32-2 ]
YieldReaction ConditionsOperation in experiment
2.1 g With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 60℃; for 36h; a) Preparation of N-[2-(ethoxycarbonyl)ethyl]-D-leucine benzyl ester[0191] D- leucine benzyl ester hydrochloride (5g) was dissolved in DMF (30ml) , DIEA (2.6g) was added, ethyl 3-bromopropionate (4.1g) was added dropwisely slowly, and the resulting mixture was allowed to react at 60C for 36h,and concentrated under reduced pressue to remove a great quantity of solvent. Ethyl acetate (20ml) was added, andthe organic phase was washed with saturated sodium hydrogencarbonate solution (50ml33) , 5% KHSO4 solution(50ml33) and water until to be neutral and washed with saturated saline solution (50ml31) , dried over anhydroussodium sulfate, and the filtrate was concentrated to give 1.57g yellow oil, which was purified on a column to give 2.1glight yellow- green oil. The content was 96% (HPLC, mobile phase 1, method 1) .Rf = 0.5Developer: petroleum ether: ethyl acetate = 2: 1Color development: ultraviolet, iodine and 1% ninhydrin solutionMS: 344 (M+Na)
In ethyl acetate; N,N-dimethyl-formamide; a) Preparation of N-[2-(ethoxycarbonyl)ethyl]-D-leucine benzyl ester <strong>[68838-94-8]D-leucine benzyl ester hydrochloride</strong> (5 g) was dissolved in DMF (30 ml), DIEA (2.6 g) was added, ethyl 3-bromopropionate (4.1 g) was added dropwisely slowly, and the resulting mixture was allowed to react at 60 C. for 36 h, and concentrated under reduced pressure to remove a great quantity of solvent. Ethyl acetate (20 ml) was added, and the organic phase was washed with saturated sodium hydrogencarbonate solution (50 ml*3), 5% KHSO4 solution (50 ml*3) and water until to be neutral and washed with saturated saline solution (50 ml*1), dried over anhydrous sodium sulfate, and the filtrate was concentrated to give 1.57 g yellow oil, which was purified on a column to give 2.1 g light yellow-green oil. The content was 96% (HPLC, mobile phase 1, method 1).
  • 18
  • [ 539-74-2 ]
  • [ 271-73-8 ]
  • [ 1467730-25-1 ]
  • [ 1467730-26-2 ]
YieldReaction ConditionsOperation in experiment
31%; 18% General procedure: A mixture of <strong>[271-73-8]1H-<strong>[271-73-8]pyrazolo[3,4-b]pyridine</strong></strong> 2 (1 eq.) and K2CO3 (10 eq.) in DMF was stirred at 80 °C. After 30 min, excess Br(CH2)nCO2Et was added and the reaction mixture was stirred for 1 h at 80 °C. Upon cooling, the mixture was acidified with 10percent aqueous HCl solution and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine and dried over anhydrous MgSO4. After filtration, the solvent was removed in vacuum and the resulting oil was purified by column chromatography (1:1 ethyl ether:petroleum ether).
  • 19
  • [ 539-74-2 ]
  • [ 148185-66-4 ]
  • ethyl 3-(4,7-dibromo-1H-benzimidazol-1-yl)propanoate [ No CAS ]
  • 20
  • [ 103361-99-5 ]
  • [ 539-74-2 ]
  • C13H14FNO4 [ No CAS ]
  • 21
  • [ 20348-09-8 ]
  • [ 539-74-2 ]
  • C12H14N2O4 [ No CAS ]
  • 22
  • [ 537033-52-6 ]
  • [ 539-74-2 ]
  • ethyl 4-(4-bromo-2,6-difluorophenyl)-4-cyanobutanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
96.5% To a solution of <strong>[537033-52-6]2-(4-bromo-2,6-difluorophenyl)acetonitrile</strong> (10 g,43.1 mmol)in THF (150 mL) was added LDA (2 M in THF,24 mL,48 mmol) dropwise in 20 min at -65 , the reaction solution was stirred for 1 hour at this temperature, then to this was added ethyl 3-bromopropanoate (9.4 g,51.7 mmol)in THF (30 mL) dropwise in 10 min. The resulting solution was stirred for 30 min at -65 , and then allowed to warm to room temperature naturally. The reaction was quenched by the addition of sat. aq. NH 4Cl (50 mL) , and extracted with EtOAc (100 mL x 3) . The combined organic layers were washed with brine, dried over anhydrous Na 2SO 4. After filtration, the filtrate was concentrated under reduced pressure to afford the product (13.8 g, 96.5%) . [M+H] + = 332.0.
96.5% To a solution of <strong>[537033-52-6]2-(4-bromo-2,6-difluorophenyl)acetonitrile</strong> (10 g,43.1 mmol)in THF (150 mL) was added LDA (2 M in THF,24 mL,48 mmol) dropwise in 20 min at -65 , the reaction solution was stirred for 1 hour at this temperature, then to this was added ethyl 3-bromopropanoate (9.4 g,51.7 mmol)in THF (30 mL) dropwise in 10 min. The resulting solution was stirred for 30 min at -65 , and then allowed to warm to room temperature naturally. The reaction was quenched by the addition of sat. aq. NH 4Cl (50 mL) , and extracted with EtOAc (100 mL x 3) . The combined organic layers were washed with brine, dried over anhydrous Na 2SO 4. After filtration, the filtrate was concentrated under reduced pressure to afford the product (13.8 g, 96.5%) . [M+H] + = 332.0.
  • 23
  • [ 2166-13-4 ]
  • [ 539-74-2 ]
  • C15H15ClN2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetone; for 12h;Reflux; General procedure: 6-Substituephenyl-3( 2H )-pyridazinonederivative(1equiva-lent), ethyl 3-bromopropionate (18.1 g, 2 equivalent) and potassiumcarbonate (13.6 g, 2 equivalent) in 50 ml acetone were heated un-der reflux for 12 h. After that, it was poured into ice water and theprecipitate was filtered off, dried and recrystallized from ethanol.
 

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Technical Information

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