Structure of Ethyl 3-bromopropionate
CAS No.: 539-74-2
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H227-H315-H319-H335 |
Precautionary Statements: | P305+P351+P338 |
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 |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.09 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.33 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.45 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.34 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.48 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.44 |
Solubility | 6.55 mg/ml ; 0.0362 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.33 |
Solubility | 8.51 mg/ml ; 0.047 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.02 |
Solubility | 1.72 mg/ml ; 0.00951 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.57 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.94 |
* 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.
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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+). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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 |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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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