Structure of Ethyl Glycolate
CAS No.: 623-50-7
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CAS No. : | 623-50-7 |
Formula : | C4H8O3 |
M.W : | 104.10 |
SMILES Code : | O=C(OCC)CO |
MDL No. : | MFCD00021970 |
InChI Key : | ZANNOFHADGWOLI-UHFFFAOYSA-N |
Pubchem ID : | 12184 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.75 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 23.79 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.36 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.17 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.46 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.39 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.03 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.18 |
Solubility | 68.7 mg/ml ; 0.66 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.35 |
Solubility | 46.3 mg/ml ; 0.445 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.12 |
Solubility | 79.2 mg/ml ; 0.76 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 |
No |
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 |
-7.06 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 |
2.0 |
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 |
0.0 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) |
1.2 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With toluene-4-sulfonic acid In toluene at 25℃; for 1 h; | To a solution of ethyl glycolate (10 g, 0.0961 mol) in toluene (100 mL) was added 3,4- dihydro-2H-pyran ( 8 g, 0.096 1 mol) followed by catalytic amount of pTSA (30 mg) and stirred at 25 °C for 1 h. After completion of the reaction, the reaction mixture was washed with water and brine solution. The organic layer was dried over anhydrous Na2504, filtered and concentrated under reduced pressure to get 18 g (99 percent) ethyl 2-((tetrahydro-2H-pyran-2- yl)oxy)acetate, 2, as colorless liquid |
94.7% | at 20℃; Industrial scale | Example 1.2Ethyl(tetrahydropyran-2-yloxy)-acetate (B) 100.00 kg (960.52 mol) ethyl glycolate (A) were dissolved in 180.0 L toluene and 365.22 g (1.92 mol) 4-toluenesulphonic acid monohydrate were added. At 20° C. a solution of 80.80 kg (960.52 mol) 3,4-dihydro-2H-pyran was added dropwise to the reaction mixture obtained and then the mixture was washed with 20.0 L toluene. The reaction mixture was stirred for 1 hour at 20° C. and after the reaction was complete it was combined with 100.0 L water and 6.53 kg (96.05 mol) ammonia solution (25percent). After phase separation the organic phase was washed with 100.0 L water and then the solvent was distilled off completely in vacuo.Yield: 188.4 kg (94.7percent of theory) |
91.5% | at 20℃; | To a stirred solution of ethyl glycolate (35.3 g, 0.339 mol) containing a few crystals of p-toluene sulfonic acid, 3,4-dihydropyran (30.0 g, 0.357 mol) was added dropwise (15 g over one hour followed by 15 g over 30 min). After stirring overnight at room temperature, the mixture was diluted with diethyl ether (80 mL) and washed with a NaHCO3 solution (from 30 mL sat. NaHCO3 and 10 mL water). The organic layer was separated and dried (Na2504) followed by evaporation of the ether. The residue was distilled under high vacuum to give 58.4 g (91.5percent) of 28 as a clear liquid. 1H NMR (CDCl3, 400 MHz)δ: 1.29 (t, 3H, J=7.1 Hz, CH3), 1.53-1.95 (m, 6H, 3,4,5-THP-CH2's), 3.50-3.55 (m, 1H, 6-THP-CH2), 3.83-3.89 (m, 1H, 6-THP-CH2), 4.19 (s, 2H, OCH2CO2R), 4.20 (t, 2H, J=7.1 Hz, CH2Me), 4.75 (m, 1H, THP-CH). 13C NMR (CDCl3, 100 MHz) δ: 14.1, 18.7, 25.2, 30.0, 60.7, 61.9, 63.8, 170.4. |
91.5% | at 20℃; | (1) Preparation of tetrahydropyran-2-yloxy-acetic acid ethyl ester (Formula 28, Scheme 4)[0378] To a stirred solution of ethyl glycolate (35.3g, 0.339mol) containing a few crystals of />toluene sulfonic acid, 3,4-dihydropyran (30.Og, 0.357mol) was added1 1 <n="113"/>dropwise (15g over one hour followed by 15g over 30min). After stirring overnight at room temperature, the mixture was diluted with diethyl ether (8OmL) and washed with a NaHCO3 solution (from 3OmL sat. NaHCO3 and 1OmL water). The organic layer was separated and dried (Na2SO4) followed by evaporation of the ether. The residue was distilled under high vacuum to give 58.4g (91.5percent) of 28 as a clear liquid. 1H NMR (CDCL3, 400MHz)δ: 1.29 (t, 3H, J = 7.1 Hz, CH3), 1.53 -1.95 (m, 6H, 3,4,5-THP-CH2's), 3.50-3.55 (m, IH, 6-THP-CH2), 3.83 - 3.89 (m, IH, 6-THP-CH2), 4.19 (s, 2H, OCH2CO2R), 4.20 (t, 2H, J = 7.1 Hz, CH2Me), 4.75 (m, IH, THP-CH). 13C NMR (CDCl3, 100MHz) δ: 14.1, 18.7, 25.2, 30.0, 60.7, 61.9, 63.8, 170.4. |
81% | With pyridinium p-toluenesulfonate In dichloromethane | Step 1) ethyl 2-(tetrahydro-2H-pyran-2-yloxy)acetate To a mixture of ethyl 2-hydroxyacetate (2 g, 20 mmol, Aldrich) and 3,4-dihydro-2H-pyran (3.2 g, 40 mmol, Alfa) in 40 mL of CH2Cl2 was added PPTS (500 mg, 2 mmol) slowly at rt. The mixture was stirred at rt for 4 hours, and then the mixture was washed with brine (20 mL*2), the combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE: EtOAc=20:1) to give colorless oil (3.01 g, 81percent). 1H NMR (400 MHz, CDCl3): δ 1.22-1.38 (m, 4H), 1.55-1.63 (m, 3H), 1.69-1.88 (m, 3H), 3.50-3.53 (m, 1H), 3.82-3.88 (m, 1H), 4.18-4.23 (m, 4H), 4.73-4.74 (t, J=4 Hz, 1H). |
81% | With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 4 h; | To a mixture of ethyl 2-hydroxyacetate (2 g, 20 mmol, Aldrich) and 3,4-dihydro-2H-pyran (3.2 g, 40 mmol, Alfa) in 40 mL of CH2Cl2 was added PPTS (500 mg, 2 mmol) slowly at rt. The mixture was stirred at rt for 4 hours, and then the mixture was washed with brine (20 mLx2), the combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residure was purified by a silica gel column chromatography (PE: EtOAc =20:1) to give colorless oil (3.01 g, 81 percent). 1H NMR (400MHz, CDCl3): δ 1.22 - 1.38 (m, 4H), 1.55 - 1.63 (m, 3H), 1.69 - 1.88 (m, 3H), 3.50 - 3.53 (m, 1H), 3.82 - 3.88 (m, 1H), 4.18 - 4.23 (m, 4H), 4.73 - 4.74 (t, J=4Hz, 1H). |
81% | With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 4 h; Inert atmosphere | To a mixture of ethyl 2 -hydroxy acetate (2 g, 20 mmol, TCI) and 3,4- dihydro-2H-pyran (3.2 g, 40 mmol, Alfa) in 40 mL Of CH2Cl2 was added PPTS (500 mg, 2 mmol, Aldrich) in portions at rt. The mixture was stirred at rt for 4 hours. The reaction mixture was then washed with brine, and the organic layer was separated and the combined organic phases were dried over Na2SO4, concentrated in vacuo. The residue was purified by a silica gel column chromatography (20: 1 (v/v) petroleum ether / EtOAc) to give the desired compound as colorless oil (3.01 g, 81 percent ).1H NMR (400MHz, CDCl3): δ 1.25 - 1.32 (m, 3H), 1.55 - 1.63 (m, 3H), 1.69 - 1.88 (m, 3H), 3.50 - 3.53 (m, IH), 3.82 - 3.88 (m, IH), 4.18 - 4.23 (m, 4H), 4.73 (t, J=3.2Hz, IH). |
58% | With toluene-4-sulfonic acid In toluene at 20℃; | Step 1 Preparation of ethyl 2-(tetrahydro-2H-pyran-2-yloxy)acetate A mixture of 3,4-dihydro-2H-pyran (20.4 g, 242.3 mmol), ethyl 2-hydroxyacetate (24.0 g, 230.8 mmol) and TsOH (0.794 g, 4.6 mmol) in toluene (150 mL) was stirred at room temperature overnight. The resulting mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (2percent EtOAc in petroleum ether) to afford ethyl 2-(tetrahydro-2H-pyran-2-yloxy)acetate (25.2 g, 58percent) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32 g | at 20℃; | EXAMPLE 1422-((l-(2-(3-Fluoro-6-methoxy-l,5-naphthyridin-4-yl)ethyl)-2- oxabicyclo[2.2.2]octan-4-ylamino)methyl)-6H-pyrimido[5,4-b][l,4]oxazin-7(8H)-oneStep 1Ethyl 2-(Tetrahydro-2H-pyran-2-yloxy)acetateTo a stirred solution of ethyl hydroxyacetate (35.3 g) containing a few crystals of p-toluene sulfonic acid, dihydropyran (30.0 g) was added dropwise. After stirring overnight at room temperature, the mixture was diluted with dichloromethane (200 mL) and washed with a sodium hydrogencarbonate solution. The organic layer was separated and dried followed by evaporation of the dichloromethane. The residue was distilled under high vacuum to give the title compound (32 g) as a clear liquid.1H NMR (CDC13): δ 1.20-1.32 (m, 3H), 1.50-1.58 (m, 3H), 1.70-1.92 (m, 3H), 3.45-3.55 (m, 1H), 3.80-3.90 (m, 1H), 4.16-4.24 (m, 4H), 4.70-4.79 (m, 1H). |
A114623 [169751-72-8]
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