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[ CAS No. 112-27-6 ] {[proInfo.proName]}

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Chemical Structure| 112-27-6
Chemical Structure| 112-27-6
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Product Details of [ 112-27-6 ]

CAS No. :112-27-6 MDL No. :MFCD00002880
Formula : C6H14O4 Boiling Point : -
Linear Structure Formula :- InChI Key :ZIBGPFATKBEMQZ-UHFFFAOYSA-N
M.W :150.17 Pubchem ID :8172
Synonyms :
Triethylene glycol

Calculated chemistry of [ 112-27-6 ]

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 7
Num. H-bond acceptors : 4.0
Num. H-bond donors : 2.0
Molar Refractivity : 35.45
TPSA : 58.92 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -8.34 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.57
Log Po/w (XLOGP3) : -1.59
Log Po/w (WLOGP) : -1.0
Log Po/w (MLOGP) : -1.13
Log Po/w (SILICOS-IT) : 0.07
Consensus Log Po/w : -0.41

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : 0.69
Solubility : 740.0 mg/ml ; 4.93 mol/l
Class : Highly soluble
Log S (Ali) : 0.86
Solubility : 1090.0 mg/ml ; 7.27 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : -0.62
Solubility : 35.9 mg/ml ; 0.239 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.25

Safety of [ 112-27-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 UN#:N/A
Hazard Statements:H315-H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 112-27-6 ]

* 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.

  • Upstream synthesis route of [ 112-27-6 ]
  • Downstream synthetic route of [ 112-27-6 ]

[ 112-27-6 ] Synthesis Path-Upstream   1~46

  • 1
  • [ 98-59-9 ]
  • [ 112-27-6 ]
  • [ 19249-03-7 ]
YieldReaction ConditionsOperation in experiment
99% With potassium hydroxide In dichloromethane at 0 - 10℃; for 3 h; General procedure: Compounds 2a–c were prepared by a modified procedure known from the literature1. Oligo ethylene glycol(37.7 mmol) and p-toluenesulfonyl chloride (14.4 g, 75.4 mmol, 2 equiv) were dissolved in dichloromethane (36 mL)and this solution was cooled to 0 °C. During permanent stirring, milled potassium hydroxide (17 g, 302 mmol, 8equiv) was added and the solution was then stirred for 3 hours while the temperature was kept from 0 to 10 °C. This reaction was monitored by TLC (UV detection). After warming up to room temperature the reaction mixture was diluted by chloroform and extracted with water (3 × 1:1). Chloroform extracts were collected, dried over magnesium sulfate overnight, filtered and solvents were evaporated under reduced pressure.
96% With potassium hydroxide In dichloromethane at 0℃; for 5 h; Triethylene glycol (2.25 g, 15 mmol) and p-toluenesulfonyl chloride (5.72 g, 30 mmol)Dissolved in 15 ml of anhydrous dichloromethane, cooled to 0 ° C, fractionated under stirring,A small amount of KOH (6.72 g, 120 mmol) was added and the temperature was maintained at 0 ° C. After stirring at 0 ° C for 5 h,The reaction was quenched by the addition of 15 ml of dichloromethane and 30 ml of ice water. Separating the organic layer,The aqueous layer was extracted twice with 15 ml of dichloromethane, the combined organic layers were washed and washed once with 10 ml of water,After drying over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure to give 6.6 g of the title compound as a white solid, yield 96percent.
94%
Stage #1: With triethylamine In dichloromethane at 20℃; for 0.333333 h;
Stage #2: With dmap In dichloromethane at 20℃; for 16 h;
To solution of triethylene glycol (3.0 g, 20.0 mmol) in dichloromethane (20 mL) was added Et3N (6.06 g, 60.0 mmol) and reaction mixture was stirred at R.T. for 20 min. To reaction mixture were added p-toluene sulfonyl chloride (7.62 g, 40.0 mmol) and DMAP (0.12 g, 1 mmol), reaction mixture was stirred at room temperature for 16 hrs. Solvent was evaporated under vacuum, residue obtained was dissolved in ethyl acetate. Ethyl acetate layer was washed with 1N-HCl, brine and dried over Na2SO4. Organic layer was concentrated and purified on flash column to obtained (ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl) bis(4-methylbenzenesulfonate) (5A) in 94 percent yield (8.58 g). 1H NMR (400 MHz, DMSO-d6) δ 7.81 (d, J = 8.2 Hz, 4H), 7.50 (d, J = 7.8 Hz, 4H), 4.13 (t, J = 4.3 Hz, 4H), 3.57 (t, J = 4.3 Hz, 4H), 3.41 (s, 4H), 2.45 (s, 6H); 13C NMR (100 MHz, DMSO-d6) δ 145.44, 132.89, 130.67, 128.15, 70.47, 70.08, 68.40, 21.61
92% With triethylamine In dichloromethane at 20℃; for 2 h; To a solution of triethylene glycol (750 mg, 1.0 equiv.) in DCM (20 mL) was added triethylamine (2.1 mL, 3.0 equiv.) then tosyl chloride (2.29 g, 2.4 equiv.) portion- wise and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was washed with saturated NH4C1 solution (20 mL x 3), then by brine. The resulting mixture was subsequently dried and evaporated. The residue was purified using flash column in the eluent of ethyl acetate/hexane (1/5, then 1/1) to give a white powder (2.11 g, 92percent). 1H NMR (500 MHz, DMSO) δ 7.77 (d, J = 8.0 Hz, 4H), 7.46 (d, J = 8.0 Hz, 4H), 4.09 (t, 4H), 3.53 (t, 4H), 3.38 (t, 4H), 2.41 (s, 6H); 13C NMR (125 MHz, DMSO) δ 145.3, 132.9, 130.6, 128.1, 70.4, 70.0, 68.3, 21.5; LCMS found m/z 459.5: (M+l).
91.4% With sodium hydroxide In tetrahydrofuran; water at 5℃; for 2 h; Large scale 16 kg (400 mol) of sodium hydroxide was dissolved in 80 L of water in a 400 L reactor, and then 18.8 L (140 mol) of triethylene glycol, 32 L of THF were added intothe reactot Afier cooling below 5° C., a solution of 47.84 kg(260 mol) of tosyl chloride and 50 L of THF was added dropwise. Following the addition, the reaction mixture waskept at this temperature for 2 hours, and it was then poured into 240 L of ice watet The precipitate was formed andfiltered, washed with a small amount of water, and dried.58.64 kg ofBPI-01 as a white crystalline powder was yielded at 91.4percent. mp: 77-80° C., HPLC: 97percent. TLC (petroleum ether:ethyl acetate=1:1) Rf=0.87.NMR data: ‘H-NMR (CDC13): ö ppm: 7.78 (d, 4H, J=10.4 Hz, benzene protons by sulfonyl group); 7.34 (d, 4H, J=1 1.6Hz, benzene protons by methyl group); 4.129 (dd, 4H, J=5.6Hz, ethylene protons by the sulfonyl group); 3.64 (dd, 4H,J=5.6 Hz, ethylene protons away from the sulfonyl group); 3.5 17 (s, 4H, ethylene protons in the middle); 2.438 (s, 6H, methyl protons on the benzene).
91.4% With sodium hydroxide In tetrahydrofuran; water at 5℃; for 2 h; Large scale Preparation: 16 kg (400 mol) of sodium hydroxide was dissolved in 80 L of water in a 400 L reactor, and then 18.8 L (140 mol) of triethylene glycol, 32 L of THF were added into the reactor. After cooling below 5° C., a solution of 47.84 kg (260 mol) of tosyl chloride and 50 L of THF was added dropwise. Following the addition, the reaction mixture was kept at this temperature for 2 hours, and it was then poured into 240 L of ice water. The precipitate was formed and filtered, washed with a small amount of water, and dried. 58.64 kg of BPI-01 as a white crystalline powder was yielded at 91.4percent. mp: 77-80° C., HPLC: 97percent. TLC (petroleum ether:ethyl acetate=1:1) Rf=0.87.
90% With potassium hydroxide In dichloromethane for 8 h; Cooling with ice The 10mL (0.075mol) of triethylene glycol,300ml dichloromethane,28.6g (0.15mol) of methyl chloride was added 500ml round-bottomed flask,Under ice-cooling,Was slowly added 33.6g (0.6mol) of potassium hydroxide,8h the reaction is substantially complete.The reaction solution was washed three times with water (3 × 100ml),The organic layer was collected,Dried over anhydrous sodium sulfate.filter,Spin dry solvent,The crude product was recrystallized from methanol,To give a white solid 30g,The yield was 90percent.
90.1% With dmap; triethylamine In dichloromethane at 20℃; for 3.5 h; Cooling with ice 434 mg of triethylene glycol (2.9 mmol) was dried in an oven at 95 ° C for 2 hours,Was dissolved in 43.5 mL of dichloromethane,1.06 g of 4-dimethylaminopyridine (8.7 mmol) and 400 μL of triethylamine (2.9 mmol)1.55 g of p-toluenesulfonyl chloride (8.1 mmol) was added under ice-cooling,Stirring for 0.5 hours, removing the ice bath and reacting at room temperature for 3 hours;15 mL of deionized water was added, extracted, the organic phase was collected, the organic phase was washed with brine (50 g / L)Add 100mg anhydrous sodium sulfate drying, filtration, rotary evaporation to remove the organic solvent,The resulting solid was purified by silica gel chromatography (eluent: dichloromethane / methanol, V / V = 9: 1) to give solid 1,2-bis (2-toluenesulfonylethoxy) ethane(Yield 90.1percent).
88%
Stage #1: With potassium hydroxide In dichloromethane at 0 - 20℃;
Stage #2: at 20℃; for 10 h;
General procedure: KOH (20 g, 356.5 mmol for 9; and 10 g, 181.5 mmol for 10–11) was added to 300 mL of a CH2Cl2 solution containing the oligoethylene glycol (10 g,94 mmol for 9, 66.6 mmol for 10, and 51.5 mmol for 11) at 0 °C. After stirring for 30 min at room temperature, TsCl (45 g, 236 mmol for 9–11) was added and the resulting solution was stirred for 10 h at room temperature. The resulting solution was filtered and then washed with aq. K2CO3. The organic layer was dried with MgSO4, filtered, and concentrated in vacuo. The resulting residue was then subjected to silicagel column chromatography (EtOAc:Hex = 1:1) to yield 35 g of 9 (90percent), 27 g of 10 (88percent), and 23 g of 11 (89percent).
87% With triethylamine In dichloromethane at 20℃; for 12 h; To a solution of 14 (4.5 g, 30.0 mmol) and TsCl (12.59 g, 66.0 mmol) in DCM (100 mL) was added NEt3 (6.68 g, 66.0 mmol). The reaction mixture was stirred at rt for 12 h and washed with water. The organic phase was dried over anhydrous Na2SO4. After removal of the solvent, the residue was purified by flash column chromatography (0-40percent EtOAc/hexanes) to afford 15 as a white solid (12.0 g, 87percent). 1H NMR (CDCl3, 600 MHz) δ 7.78 (d, J = 7.8 Hz, 4H), 7.34 (d, J = 7.8 Hz, 4H), 4.19-4.10 (m, 4H), 3.70-3.62 (m, 4H), 3.57-3.48 (m, 4H), 2.44 (s, 6H). HRMS (ESI+) calcd for C20H26NaO8S2 (M+Na)+ 481.0961, found 481.0963.
87% With triethylamine In dichloromethane at 20℃; for 8 h; p-toluenesulfonyl chloride (40.63 g, 213.09 mmol) was dissolved in methylene chloride (MC, 150 mL) in a 500 mL 1 neck round flask and, then, triethyleneglycol (16 g, 105.55 mmol) and triethylamine (29.72 mL, 213.09 mmol) were added. The reacting mixture was stirred at room temperature for 8 hr. After reaction, 200 mL of distilled water was added and extraction was carried out by using 600 mL of chloroform (CHCl3). After removing the solvents, products were separated by column chromatography (silica, hexane/ethyl acetate=1:1 (v/v)). (yield=42.59 g, 87percent)1H NMR (400 MHz, CDCl3): δ 7.80-7.78 (d, 4H), 7.35-7.33 (d, 4H), 4.15-4.12 (t, 4H), 3.66-3.64 (t, 4H), 3.52 (s, 4H), 2.44 (s, 6H). (See, FIG. 9).
76% With triethylamine In tetrahydrofuran at 20℃; for 12 h; Inert atmosphere To a solution of triethylene glycol (6 g, 40.00 mmol) in THF (80 mL) was added Et3N (10.12 g, 100.00mmol). Tosyl chloride (15.6 g, 80.00 mmol) was added and stirred at room temperature for 12 h. Thesolvent was removed under reduced pressure and the residue was dissolved in EtOAc. The organic layerwas washed with aqueous 1N HCl and brine. The organic layer was dried over Na2SO4, and concentratedunder reduced pressure. The crude residue was purified by flash column chromatography (EtOAc: Hexane= 10: 1) to afford compound 19 as a clear colorless oil in 76 percent yield (14 g). This compound was alreadyreported.2 1H NMR (400 MHz, DMSO-d6) δ 7.81 (d, J = 8.2 Hz, 4H), 7.50 (d, J = 7.8 Hz, 4H), 4.13 (t, J =4.3 Hz, 4H), 3.57 (t, J = 4.3 Hz, 4H), 3.41 (s, 4H), 2.45 (s, 6H); 13C NMR (100 MHz, DMSO-d6) δ 144.89,132.38, 130.13, 127.63, 69.98, 69.82, 69.70, 69.65, 69.19, 67.86, 65.53, 21.09, 15.11. ESI-MS: m/z = 459(M + H)+.
64% With triethylamine In diethyl ether at 20℃; for 18 h; Inert atmosphere To a solution of triethylene glycol (3 g, 0.02 mol) in diethyl ether (40 mL), triethylamine (7.8 g, 0.04 mol) was added at room temperature, followed by addition of p-toluenesulfonyl chloride (7.8 g, 0.04 mol) under argon atmosphere. The mixture was stirred at room temperature for 18 h (TLC monitoring, ethyl acetate/hexanes, 1:4). The organic solvents were removed under reduced pressure. The residue was dissolved in methylene chloride (20 mL), washed with sodium bicarbonate (20 mL, saturated), water (20 mL .x. 2), brine (30 mL), dried over magnesium sulfate and concentrated under vacuum. Colorless crystals of triethylene glycol ditosylate were obtained from ethyl acetate.Yield = 5.8 g, 64percent mp: 75-77 °C. Rf = 0.5 (ethyl acetate/hexanes, 1:4). 1H NMR (300 MHz, CDCl3): δ 7.78 and 7.34 (AA'BB', 8H), 4.12 (d, 4H), 3.65 (t, 4H), 3.53 (s, 4H), 2.45 (s, 6H). 13C NMR (75 MHz, CDCl3, δ 145.1, 133.3, 130.1, 128.2, 70.9, 69.4, 69.0, 21.8.
13.74 g With sodium hydroxide In tetrahydrofuran; water 5 g (33.3 mmol) of triethylene glycol and 13.96 g (73.2 mmol) of 4-toluenesulfonyl chloride were dissolved in tetrahydrofuran 100ml and stirred. Then, 4.66 g (116.5 mmol) of sodium hydroxide was dissolved in the minimum amount of water," After completion of the reaction, diethyl ether and water were added to separate the layers, and the mixture was concentrated under reduced pressure,To give 13.74 g (29.97 mmol) of the titled compound.

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Reference: [1] Yakugaku Zasshi, 1944, vol. 64, p. 295 - 298[2] Chem.Abstr., 1951, p. 5104
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Reference: [1] Patent: US2798873, 1953, ,
[2] Synthetic Communications, 1986, vol. 16, # 1, p. 19 - 26
[3] Journal of Organic Chemistry, 1992, vol. 57, # 24, p. 6678 - 6680
[4] Angewandte Chemie - International Edition, 2015, vol. 54, # 12, p. 3763 - 3767[5] Angew. Chem., 2015, vol. 127, # 12, p. 3834 - 3838,5
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Reference: [1] Canadian Journal of Research, Section B: Chemical Sciences, 1936, vol. 14, p. 80
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[2] Helvetica Chimica Acta, 1991, vol. 74, # 8, p. 1697 - 1706
[3] Inorganica Chimica Acta, 2011, vol. 365, # 1, p. 38 - 48
[4] European Journal of Organic Chemistry, 2011, # 9, p. 1641 - 1644
[5] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 2, p. 1151 - 1155
[6] European Journal of Organic Chemistry, 2013, # 35, p. 7952 - 7959
[7] Angewandte Chemie - International Edition, 2015, vol. 54, # 35, p. 10327 - 10330[8] Angew. Chem., 2015, vol. 35, # 37, p. 10467 - 10471,5
[9] Patent: EP3127900, 2017, A1,
[10] Chinese Chemical Letters, 2017, vol. 28, # 4, p. 832 - 838
[11] Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3498 - 3510
[12] Bioconjugate Chemistry, 2017, vol. 28, # 9, p. 2284 - 2292
[13] Patent: CN104725453, 2017, B,
[14] Patent: EP3321279, 2018, A1,
[15] Chinese Chemical Letters, 2018,
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Reference: [1] Patent: US2412209, 1943, ,
[2] Patent: US2357176, 1940, ,
[3] Patent: US2412209, 1943, ,
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  • [ 112-27-6 ]
  • [ 23243-68-7 ]
YieldReaction ConditionsOperation in experiment
85% at 150℃; for 24 h; Ethylenedioxydiethanol: chloroacetic acid molar ratio of 1: 2
To a 50mL three-neck round bottom flask equipped with a magnetic stirrer, a reflux condenser and a thermometer, add ethylenedioxydiethanol (1mmol) and chloroacetic acid (2mmol). Start the stirring at 150 deg.C. React for 24 hours. After completion of the reaction, the reaction solution was cooled to room temperature, the resulting precipitate was added to 100mL of hot methanol, and stirred to dissolve, filtered, and the filtrate was slowly volatilize give a white solid, yield 85percent;
Reference: [1] Patent: CN105669707, 2016, A, . Location in patent: Paragraph 0018; 0019
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Reference: [1] Synlett, 2007, # 17, p. 2691 - 2694
[2] Tetrahedron, 2009, vol. 65, # 34, p. 7177 - 7185
[3] Russian Journal of Organic Chemistry, 2012, vol. 48, # 8, p. 1047 - 1054[4] Zh. Org. Khim., 2012, vol. 48, # 8, p. 1051 - 1058,8
[5] RSC Advances, 2015, vol. 5, # 126, p. 103782 - 103789
[6] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1981, vol. 17, # 8, p. 847 - 852[7] Khimiya Geterotsiklicheskikh Soedinenii, 1981, # 8, p. 1132 - 1137
[8] Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical & Analytical, 1982, vol. 21, # 5, p. 520 - 522
[9] Annales de Chimie (Cachan, France), 1863, vol. <3> 69, p. 321[10] Justus Liebigs Annalen der Chemie, 1862, vol. 122, p. 354
[11] Tetrahedron, 1982, vol. 38, # 14, p. 2055 - 2060
[12] Patent: WO2012/40204, 2012, A2, . Location in patent: Page/Page column 29
  • 22
  • [ 62921-74-8 ]
  • [ 112-27-6 ]
  • [ 23601-40-3 ]
YieldReaction ConditionsOperation in experiment
69% at 100℃; for 12 h; 2-(2-(2-Methoxyethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (Al, 1.0 g, 3.14 mmol) was added with stir to triethylene glycol (2.10 mL, 15.7 mmol). Potassium hydroxide (510 mg, 9.42 mmol) was ground into a powder and added to the reaction and the mixture refluxed at 100°C for 12 hours, upon which the reaction was diluted with water (50 mL) and extracted with DCM. The organic layers were combined, dried over sodium sulfate, and concentrated under reduced pressure to obtain 2,5,8,1 l,14,17-hexaoxanonadecan-19-ol as a yellow oil in 69percent yield.
65% Reflux The synthesis of compound 3 is shown in Figure 5. Synthesis of compound 3 began by coupling tosylate (6) to triethylene glycol (16) under basic conditions to yield hexaethylene glycol monomethyl ether (17) in 65percent yield. Hexaethylene glycol monomethyl ether (17) was then converted to the corresponding tosylate (18) in 77percent yield, followed by conversion to the azide. The azide was reduced to the corresponding amine (19) via a hydrogenation over activated palladium on carbon in 45percent yield. The amine was coupled to cyanoacetic acid using 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in 80percent yield to give the cyano-acetamide (20). The resulting amide (20) was coupled with previously synthesized piperidine-naphthalene (12) to give compound 3 via Knovenagel condensation in 61percent yield.
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[2] Organic Letters, 2004, vol. 6, # 4, p. 469 - 472
[3] Patent: WO2015/143185, 2015, A1, . Location in patent: Paragraph 00819
[4] Patent: WO2016/40891, 2016, A2, . Location in patent: Paragraph 00316
[5] Bulletin of the Korean Chemical Society, 2011, vol. 32, # 7, p. 2193 - 2198
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Reference: [1] Molecular Crystals and Liquid Crystals (1969-1991), 1988, vol. 160, p. 331 - 338
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Reference: [1] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 24, p. 10295 - 10300
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Reference: [1] Chemistry - An Asian Journal, 2011, vol. 6, # 2, p. 452 - 458
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Reference: [1] Bulletin of the Chemical Society of Japan, 1978, vol. 51, p. 3111 - 3120
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Reference: [1] Science China Chemistry, 2010, vol. 53, # 12, p. 2452 - 2460
[2] Journal of the American Chemical Society, 1943, vol. 65, p. 23,25[3] Journal of the American Chemical Society, 1948, vol. 70, p. 214,215
[4] Journal of the American Chemical Society, 1943, vol. 65, p. 23,25[5] Journal of the American Chemical Society, 1948, vol. 70, p. 214,215
[6] Journal of the American Chemical Society, 1943, vol. 65, p. 23,25[7] Journal of the American Chemical Society, 1948, vol. 70, p. 214,215
[8] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 7, p. 2443 - 2450
[9] Patent: US2437905, 1945, ,
[10] Patent: US2372808, 1941, ,
[11] Patent: US2401607, 1944, ,
[12] Patent: US2437905, 1945, ,
[13] Patent: US2372808, 1941, ,
[14] Patent: US2401607, 1944, ,
[15] Patent: US2437905, 1945, ,
[16] Patent: US2372808, 1941, ,
[17] Patent: US2401607, 1944, ,
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Reference: [1] Journal of Organic Chemistry, 1999, vol. 64, # 18, p. 6870 - 6873
[2] Synthetic Communications, 1986, vol. 16, # 1, p. 19 - 26
[3] Journal of Organic Chemistry, 1992, vol. 57, # 24, p. 6678 - 6680
[4] Angewandte Chemie - International Edition, 2015, vol. 54, # 12, p. 3763 - 3767[5] Angew. Chem., 2015, vol. 127, # 12, p. 3834 - 3838,5
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Reference: [1] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 7, p. 2443 - 2450
  • 30
  • [ 100-44-7 ]
  • [ 112-27-6 ]
  • [ 55489-58-2 ]
YieldReaction ConditionsOperation in experiment
67%
Stage #1: With sodium hydroxide In water for 0.166667 h;
Stage #2: at 100℃;
Triethylene glycol (30 g, 0.2 mol) was dissolved in a solution of NaOH (8 g in 8 mL of H2O) and stirred for 10 min. Then benzyl chloride (7 mL, 0.062 mol) was added and the reaction mixture was heated to 100° C. and stirred overnight. The crude reaction was diluted with sat NaCl (500 mL), washed CH2Cl2 (2.x.400 mL), organic layers dried MgSO4, and evaporated to dryness. Column chromatography (silica, ethyl acetate to ethyl acetate/MeOH, 10:1) afforded 1 a yellowish oil (9.87 g, 67percent yield).
Reference: [1] European Journal of Organic Chemistry, 2008, # 17, p. 2900 - 2914
[2] Journal of the American Chemical Society, 2013, vol. 135, # 25, p. 9248 - 9251
[3] Synthetic Communications, 1986, vol. 16, # 1, p. 19 - 26
[4] Tetrahedron Letters, 2001, vol. 42, # 23, p. 3819 - 3822
[5] Patent: US2008/207505, 2008, A1, . Location in patent: Page/Page column 31
[6] Journal of Chemical Research, Miniprint, 1984, # 9, p. 2672 - 2691
[7] Journal of Organic Chemistry, 1994, vol. 59, # 25, p. 7695 - 7700
[8] Analytical Chemistry, 1992, vol. 64, # 15, p. 1685 - 1690
[9] Journal of Pharmaceutical Sciences, 1975, vol. 64, # 4, p. 693 - 695
[10] Arzneimittel-Forschung, 1978, vol. 28, # 11, p. 2061 - 2063
[11] Synthetic Communications, 1990, vol. 20, # 6, p. 799 - 807
[12] Journal of the Chemical Society, Chemical Communications, 1990, # 13, p. 911 - 912
[13] Liebigs Annalen der Chemie, 1992, # 10, p. 1029 - 1032
  • 31
  • [ 100-39-0 ]
  • [ 112-27-6 ]
  • [ 55489-58-2 ]
YieldReaction ConditionsOperation in experiment
92.9% With silver(l) oxide In dichloromethane for 2 h; Inert atmosphere Ag2O (6.9 g, 30 mmol) was added to a solution of triethylene glycol (3.0 g, 20 mmol) in dry CH2Cl2. BnBr (2.6 mL, 22 mmol) was then added dropwise over 5 min, and the mixture was stirred for 2 h. After this time, the suspension was filtered through a pad of Celite, which was thoroughly washed with CH2Cl2. The combined filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography to yield a yellow oil (4.46 g, 92.9percent). 1H NMR (300 MHz, CDCl3): δ 7.26-7.35 (m, 5H, Ph), 4.56 (s, 2H, -CH2Ph), 3.73-3.58 (m, 12H, -OCH2CH2O-), 2.80 (br, 1H, -OH); 13C NMR (75 MHz, CDCl3): δ 138.0, 128.2, 127.6, 127.5, 73.1, 72.4, 70.5, 70.4, 70.2, 69.2, 61.5.
36%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil for 1 h; Inert atmosphere
Stage #2: at 0 - 20℃; for 16 h; Inert atmosphere
General procedure: Sodium hydride (60percent dispersion in mineral oil, 0.5 equiv) wasadded portion-wise to a solution of triethyleneglycol (1 equiv.) inTHF (50 mL) under nitrogen. The reaction was stirred for 1 h andthen cooled to 0 C. Benzyl bromide (0.5 equiv.) was then addeddrop-wise, and the reaction mixture was warmed to room temperatureand then stirred for 16 h. The reaction mixture was cooledin an ice bath quenched by the addition of methanol (20 mL), andthen concentrated in vacuo. The residue was dissolved in DCM(30 mL), and washed with water (30 mL). The combined organicextracts were dried over anhydrous MgSO4, filtered, and concentratedin vacuo, to afford a yellow oil, which was purified by flashchromatography.
Reference: [1] Tetrahedron, 2012, vol. 68, # 35, p. 7148 - 7154
[2] Journal of Organic Chemistry, 2004, vol. 69, # 3, p. 639 - 647
[3] Organic and Biomolecular Chemistry, 2009, vol. 7, # 6, p. 1064 - 1067
[4] Organic and Biomolecular Chemistry, 2009, vol. 7, # 18, p. 3652 - 3656
[5] Journal of Organic Chemistry, 2012, vol. 77, # 20, p. 8879 - 8887
[6] Chemical Communications, 2007, # 47, p. 5066 - 5068
[7] Chemistry - A European Journal, 2017, vol. 23, # 56, p. 13875 - 13878
[8] European Journal of Medicinal Chemistry, 2015, vol. 102, p. 153 - 166
[9] Carbohydrate Research, 1992, vol. 230, # 1, p. 117 - 149
[10] Journal of the American Chemical Society, 1994, vol. 116, # 12, p. 5057 - 5062
[11] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1994, # 5, p. 989 - 1002
[12] Analytical Chemistry, 1996, vol. 68, # 1, p. 208 - 215
[13] Canadian Journal of Chemistry, 2010, vol. 88, # 12, p. 1222 - 1232
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Reference: [1] Journal of Organic Chemistry, 2006, vol. 71, # 26, p. 9884 - 9886
  • 33
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Reference: [1] Tetrahedron Letters, 1997, vol. 38, # 34, p. 5945 - 5948
  • 34
  • [ 128-39-2 ]
  • [ 112-27-6 ]
  • [ 4130-42-1 ]
  • [ 4973-24-4 ]
  • [ 96469-23-7 ]
  • [ 128-37-0 ]
  • [ 5427-03-2 ]
  • [ 3673-68-5 ]
  • [ 39169-63-6 ]
  • [ 96-70-8 ]
  • [ 5530-30-3 ]
Reference: [1] Russian Journal of General Chemistry, 2008, vol. 78, # 9, p. 1728 - 1733
  • 35
  • [ 98-59-9 ]
  • [ 112-27-6 ]
  • [ 77544-68-4 ]
YieldReaction ConditionsOperation in experiment
89% With sodium hydroxide In tetrahydrofuran; water at 0℃; for 2 h; Triethylene glycol (16.81 g, 112 mmol) was dissolved in 20 mL THF, NaOH solution (6.73 g, 168 mmol in 15 mL H2O). The mixture was cooled down to 0 °C by ice/water bath, then TsCl (25.67 g, 135 mmol) in THF (150) was added dropwise to the mixture and the reaction was started simultaneously. The solution was stirred for another 1 h and the solvent was evaporated. The residue was dissolved in DCM and washed with brine (if there is a lot of salt we can wash first the organic layer with water). After that drying over MgSO4, the crude product was further purified by column chromatography with hexane/ethylacetate (2:1) as eluant, afforded the product as yellow oil; yield: 89percent. 1H NMR (CDCl3): δ = 2.44 (s, 3H, CH3), 3.51-3.70 (m, 12H, 6CH2), 7.34 (d, 2H, Ar-H), 7.80 (d, 2H, Ar-H). MS (MALDI-TOF): m/z calc, 304.1; found, 327.21 [M + Na]+.
88.3% With sodium hydroxide In tetrahydrofuran; water at 20℃; for 6 h; Cooling with ice (3) Take the flask, add 0.532 mοl triethylene glycol, add 50 mL of tetrahydrofuran, then slowly drop the cooled 0.2 moles of aqueous sodium hydroxide solution, stir the mixture for several minutes, Under the addition of 0.134 mol of p-methanesulfonyl chloride solution, one hour after the drop, after the completion of the drop of ice water removed, to room temperature reaction, 5 hours after the reaction to remove the solvent to get white or light yellow liquid, dissolved with ethyl acetate, saturated aqueous sodium chloride solution several times, combined with organic phase anhydrous magnesium sulfate drying. The solvent was removed by filtration to give a colorless or pale yellow oil which yielded 88.3percent yield.
83.94% With triethylamine In dichloromethane 250mL single-neck flask was added triethylene glycol (19.69g, 131.13mmol), solution of p-toluenesulfonyl chloride (5.00g triethylamine (7.96g, 78.68mmol) and dichloromethane (50mL), ice-cooled, 26.23 mmol) was dissolved in dichloromethane (50 mL) of. After completion of the dropwise addition, the reaction system was transferred to room temperature overnight. The solvent was removed by rotary evaporation, the residue was added methylene chloride (a 500 mL) was dissolved, washed with water (a 500 mL) and saturated brine (300mL), dried over anhydrous sodium sulfate. Filtered and the solvent was removed by rotary evaporation to give a colorless oil 6.70g, yield 83.94percent.
79% With N-ethyl-N,N-diisopropylamine In dichloromethane at 5 - 20℃; for 18 h; FIG. 10A shows the synthesis of compound 1. Tosyl chloride (1.00 g, 5.25 mmol) was added at 5° C. to a solution of TEG (triethylene glycol, 1.57 g, 10.5 mmol) in anhydrous methylene chloride (6 mL). This was followed by drop-wise addition of DIPEA (N,N-diisopropylethylamine, 1.0 mL, 5.77 mmol). The water bath was removed and the reaction mixture stirred at room temperature for 18 hours. The resulting mixture was diluted with water (6 mL) and washed with 1 M HCl, brine (2×10 mL), and water (3×10 mL). The solution was dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by silica gel chromatography (ethyl acetate/hexane 7:3) to obtain the product as yellow oil (1.26 g, 79percent). LEN et al., “Micellar Catalysis Using a Photochromic Surfactant: Application to the Pd-Catalyzed Tsuji-Trost Reaction in Water” J. Org. Chem., 79(2): 493-500 (2014). FIG. 10B shows the 1H NMR 300 of compound 1 CDCl3.
75% With pyridine In dichloromethane at 20℃; for 18 h; Briefly, p-toluenesulfonyl chloride (7.50 g, 40.0 mmol) was added to a solution of triethylene glycol (60.0 g, 40.0 mmol) in pyridine (6.5 mL) and dichloromethane (400 mL) and under nitrogen.
After stirring for 18 hr at room temperature, the solvent was concentrated under reduced pressure.
The residue was dissolved in ethyl acetate (200 mL) and washed with aq. NaCl solution (3*200 mL).
The aq.
extract was back extracted with ethyl acetate (2*100 mL), and the combined ethyl acetate phases were dried over MgSO4.
After filtering and evaporating to dryness the product was purified on a silica column to yield a clear oil (9.30 g, 75percent).
1H NMR (300 MHz, CDCl3, TMS): δ 7.82 (d, 3JHH=8.1 Hz, 2H), 7.36 (d, 3JHH=8.1 Hz, 2H), 7.19 (t, 3JHH=3.6 Hz, 2H), 3.59-3.78 (m, 10H), 2.47 (s, 3H).
13C NMR (75 MHz, CDCl3, TMS): δ 144.86, 132.93, 129.82, 127.96, 72.48, 70.77, 70.34, 69.13, 68.70, 61.74, 21.62. IR (NaCl): v=3421, 2886, 1594, 1358, 1169, 664 cm31 1.
75% With potassium hydroxide In tetrahydrofuran at 20℃; for 5 h; Compound 6-1 (235 g, 1.57 mol) was dissolved in 500 mL of tetrahydrofuran, then potassium hydroxide (41.2 g, 0.57 mmol, 82percent w/w) was added, and then p-toluenesulfonyl chloride 6-2 (100 g, 0.52 mol) was added in batches, and the mixture was stirred at room temperature for 5 hours. The reaction solution was poured into 1200 mL of water, and extracted with ethyl acetate (400 mL*3). The extract liquid was combined and washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure and purified by silica gel column chromatography, with an eluent (petroleum ether:ethyl acetate=1:1), to obtain the target product 6-3 (118 g, 75percent) as a colorless oil. LC-MS: m/z=305[M+H]+.
71% With triethylamine In dichloromethane at 20℃; for 12 h; Inert atmosphere; Cooling with ice The reaction process is as follows: three glycol (262.0mmol), triethylamine (40mmol) and methylene chloride (30 ml) mixed and placed in a 250 ml three flasks; will be to toluene sulfonyl chloride (26mmol) and methylene chloride (35 ml) is placed in the dropping funnel constant and is dropped in the three-mouth flask. The use of balloon under the protection of nitrogen ice salt bath stirring, all melted ice when the temperature of the into stirring at the room temperature, the total reaction time is about 12h. Using thin layer chromatography (TLC) detecting the extent of reaction. When the TLC display in the reactant material point recedes, stopping the reaction. The reaction mixture is cooled to room temperature, water washing three times, the aqueous phase dichloromethane is used for extraction, the combined organic phase with anhydrousMgSO4drying, filtering, then turns on lathe reducing the organic solvent. The final 100 - 200 mesh silica gel column chromatography separation method of purification. The ethyl acetate: dichloromethane=4:1 (V/V) as eluant. At the end of the colorless transparent oily liquid product 5.65g (18.6mmol), yield 71percent.
71.3% With pyridine In dichloromethane at 20℃; for 18 h; Inert atmosphere p-Toiuenesuifonyi chloride (7.50 g, 40.0 mrnoi) was added to a solution oftriethylene glycol (60.0 g, 40.0 mrnoi) in pyridine (6.5 mE) and dichiorornethane (DCM, 400 mL) and under nitrogen. After stirring at room temperature for 18 h, the solvent was removed via rotovap. The residue was dissolved in ethyl acetate (200 rnL) and washed with brine (3x100 mL). The ethyl acetate solution was dried over anhydrous Na2SO4. After filtration, the filtrate was evaporated to dryness to give crude product which was puxfied on a silicacolumn to yield 8-tosyloxy-3,6-dioxooctan-I-ol as a clear oil (868 g, 713percent). Orbitrap ESIMS Caicd. for C13H2O6S 30410 Found 305.11.
60% With triethylamine In tetrahydrofuran at 0 - 25℃; for 18 h; Tnethylene glycol (120 mmol, 3 eq.) was dissolved in anhydrous THF (80 ml) and triethylamine (80 mmol, 2 eq.) was added. At 0 °C p-toluenesulfonyl chloride (40 mmol, 1 eq.) in anhydrous THF (10 ml) wasadded dropwise over 45 mm. The reaction mixture was allowed to warm to room temperature and stirred overnight. The solvent was then removed in vacuo and the crude mixture purified by flash column chromatography using a gradient from 30percent-90 percent Ethyl acetate in heptane.
48% With triethylamine In dichloromethane at 25℃; for 12 h; Triethylene glycol (4.50 g, 30 mmol) and triethylamine (TEA) (8.0 mL) were dissolved in dichloromethane (60 mL). Then, tosylchloride (5.70 g, 30 mmol) was added in one portion. The resulting mixture was stirred for 12 h at 25 oC (Scheme 2). After washing with KHSO4 (1 mol/L, 40 mL) and NaHCO3 (5percent, 40 mL) and drying over anhydrous Na2SO4, the crude product was obtained by evaporation and subsequently purified by column chromatography over silica gel (dichloromethane/MeOH = 100:1, v/v) to obtain the target product 1 as a colorless oil (4.2 g, 14.4 mmol, 48percent).
44.4% With dmap; triethylamine In tetrahydrofuran at 0 - 20℃; for 13 h; To a solution of compound 1 (100 g, 665.90 mmol) in THF (500 ml), was added Et3N (46.15 ml, 332.95 mmol) and DMAP (6.51 g, 53.27 mmol) at r.t. Then PTSC (63.48 g, 332.95 mmol) in THF (200 ml) was dropped to above mixture solution for 1h and stirred at 0 °C. Next the mixture solution was stirred for about 12 h at r.t. The reaction mixture was filtered through a celite pad to remove Et3N.HCl. The solvent was evaporated under vacuum. The crude material was purified by column chromatography (DCM : MeOH = 80:1) to obtain yellow oil (90 g , yield 44.4percent). 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H), 4.22 –4.13 (m, 2H), 3.76 –3.67 (m,4H), 3.62 (s, 4H), 3.60 –3.56 (m, 2H), 2.45 (s, 3H), 2.05 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 144.9, 132.7, 129.8, 127.9, 72.5, 70.6, 70.1, 69.2, 68.5, 61.5, 21.6.
33% With potassium iodide; silver(l) oxide In dichloromethane at 20℃; Into a 250-mL round-bottom flask, was placed a solution of 2-[2-(2-hydroxyethoxy)ethoxy]-ethan-1-ol (1.5 g, 9.99 mmol, 1.00 equiv), Ag2O (3.4 g, 14.98 mmol, 1.50 equiv), KI (0.5 g, 2.99 mmol, 0.30 equiv) in dichloromethane (50 mL) at room temperature. This was followed by the addition of TsCl (2.3 g, 12.06 mmol, 1.20 equiv). The resulting solution was stirred overnight at room temperature. The reaction mixture was then quenched by the addition of water (40 mL). The insoluble solids in the reaction mixture were filtered out and the filtrate was extracted with dichloromethane (40 ml x 3). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was applied onto a silica gel column during with dichlorome thane/me thanol (1 : 1). This resulted in 1 g (33percent) of 14-[(4-methylbenzenesulfonyl)oxy]-3,6,9,12-tetraoxatetradecan-1-ol as yellow oil.
30%
Stage #1: With sodium hydroxide In tetrahydrofuran at 0℃; for 0.25 h;
Stage #2: at 20℃; for 2 h;
j00524j A solution of triethylene glycol (30 g, 199.7 mmol) in THF (300 mL) wascooled to 0°C and charged with NaOH (11.98 g, 299.7 mmol) and stirred for 15 mm. Thissolution was charged with tosyl chloride (38.07 g, 199.7 mmol) and stirred at room temperature for 2 h. The reaction mixture was concentrated in vacuo and the residue obtained was dilutedwith water (100 mL) and extracted with ethyl acetate (3 X 200 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo resulting in acrude compound which was purified by chromatography on silica gel, eluting with 2percentmethanol in DCM to give 18.5 g, 30percent yield of the title compound as a colorless oil. ‘H NMR(400 MHz, CDC13): ö = 7.78 (d, J= 8.3 Hz, 2H), 7.33 (d, J= 8.1 Hz, 2H), 4.25 —4.10 (m, 2H),3.75 — 3.60 (m, 6H), 3.63 — 3.52 (m, 4H), 2.43 (s, 3H).
22% With dmap; triethylamine In dichloromethane at 0 - 20℃; for 4 h; Inert atmosphere General procedure: p-TsCI (1.2 eq.) was added dropwise to a mixture of the appropriate di-alcohol, Et3N (1 eq.), and DMAP (cat.) in dry CH2CI2 (0.01 M) under N2 atmosphere with stirring at 0°C. The stirring was continued at room temperature for 4 hours. The reaction was quenched with saturated NH4CI aqueous solution and the whole was extracted with AcOEt. The extract was washed with brine, dried over Na2SO4, and, following solvent evaporation, the crude was purified by flash chromatography. ES154; 2-(2-(2-hydroxyethoxy)ethoxy)ethyl 4-methylbenzenesu Ifonate. It was synthesized from triethylene glycol (1 .000 g, 6.66 mmol). Elution with petroleum etherAcOEt (2:8) afforded ES154 as a waxy solid: 0.450 g (22percent).1H-NMR (CDCI3, 400 MHz)5 2.30 (s, 3H), 2.99 (br s, exchangeable with D20, IH), 3.40-3.63 (m, IOH), 4.02 (t,J=4.8 Hz, 2H), 7.21 (d, J=8.4 Hz, 2H), 7.64 (d, J=8.4 Hz, 2H). 13C-NMR (CDCI3, 100MHz) 521.48, 42.73, 61.39, 68.47, 69.24, 70.06, 70.42, 71.12, 72.46, 127.79, 129.81,132.71, 144.87.
55 g at 0 - 20℃; Inert atmosphere Under the protection of nitrogen, to a 1000ml three-necked flask were added 200 mL pyridine, 120 g BP103a00(1.0eq), stirred and cooled down to 0°C. 151.8g TsCl (1.0eq) was added in batches, stirred for 1h, then slowly warmed up to room temperature, and kept stirring for 3-4h. After the completion of the reaction, the reaction liquid was poured into ice-cold dilute hydrochloric acid solution, extracted with ethyl acetate. The ethyl acetate layer was washed once with dilute hydrochloric acid, washed with saturated sodium bicarbonate, washed with saturated brine, and dried over anhydrous Na2SO4. The solvents were evaporated off at reduced pressure, and chromatographed in a silica gel column to give 55g pure BP103a01.

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YieldReaction ConditionsOperation in experiment
96%
Stage #1: With sodium In tetrahydrofuran at 20℃;
Stage #2: at 20℃; for 20 h;
Stage #3: With hydrogenchloride; water In tetrahydrofuran
Synthesis of Compound 71; Step a: Sodium (0.10 g, 4.35 mml) was added to a solution of triethyleneglycol (64.0 mL, 0.48 mol) in anhydrous THF (250 mL) at room temperature. tert-Butyl acrylate (24.0 mL, 0.164 mol) was added after the sodium was dissolved. The reaction mixture was stirred at room temperature for 20 h and neutralized with 1.0 N HCl (4 mL). After removal of the solvent, the residue was suspended in brine and extracted with EtOAc (3.x.70 mL). The combined organic layers were washed with brine and dried over MgSO4. After evaporation of the solvent, the tert-butylacylate adduct (40.23 g, 0.157 mol, 96percent) was a colorless oil, which was used directly for the next reaction step without further purification. HPLC: tR=10.2 min.
95.5% With sodium In tetrahydrofuran at 20℃; for 24 h; 250mL round bottom flask was added 2- (2- (2-hydroxyethoxy) ethoxy) ethanol (37.00mL, 276.9mmol) was dissolved in dry tetrahydrofuran (150 mL) and stirred under addition of sodium (55mg, 2.39 mmol), at room temperature, followed by dropwise addition of tert-butyl acrylate (11.30mL, 77.8mmol) to the reaction system, the reaction system was reacted at room temperature for 24 hours. Completion of the reaction system with 1mol / L dilute hydrochloric acid to the pH adjusted to 7. And (300mL × 3) and extracted with ethyl acetate, the organic layer was washed with saturated brine (100mL × 3), dried the combined organic phases were dried over anhydrous sodium sulfate, filtered and the solvent under reduced pressure to give a spin yellow oily liquid 20.7g, yield: 95.5percent.
84% With sodium In tetrahydrofuran at 20℃; Into a 1000-mL round-bottom flask, was placed a solution of 2,2'-(2,2'-oxybis(ethane-2,1-diyl)bis,2-diylbis(oxy))diethanol (82 g, 546.05 mmol, 3.50 equiv) in tetrahydrofuran (300 mL), sodium (110 mg, 4.78 mmol, 0.03 equiv).
This was followed by the addition of tert-butyl acrylate (20 g, 156.04 mmol, 1.00 equiv) dropwise with stirring at room temperature.
The resulting solution was stirred overnight at room temperature.
The pH value of the solution was adjusted to 7 with 1M hydrochloric acid.
The resulting solution was extracted with 3*100 mL of ethyl acetate and the organic layers combined.
The resulting mixture was washed with 3*100 mL of brine.
The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum.
This resulted in 36.6 g (84percent) of tert-butyl 3-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)propanoate as yellow oil.
79%
Stage #1: With sodium In tetrahydrofuran
To a solution of 2,2’-(ethane-1,2-diylbis(oxy))diethanol (55.0 mL, 410.75 mmol, 3.0 eq.) in anhydrous THF (200 mL) was added sodium (0.1 g). The mixture was stirred until Na disappeared and then tert-butyl acrylate (20.0 mL, 137.79 mmol, 1.0 eq.) was added dropwise. The mixture was stirred overnight and then quenched by HCl solution (20.0 mL, 1N) at 0 °C. THF was removed by rotary evaporation, brine (300 mL) was added and the resulting mixture was extracted with EtOAc (3 × 100 mL). The organic layers were washed with brine (3 × 300 mL), dried over anhydrous Na2SO4, filtered and concentrated to afford a colourless oil (30.20 g, 79.0percent yield), which was used without further purification. MS ESI m/z calcd for C13H27O6 [M + H]+ 278.1729, found 278.1730.
79% With sodium In tetrahydrofuran To a solution of 2,2' -(ethane- l,2-diylbis(oxy))diethanol (55.0 mL, 410.75 mmol, 3.0 eq.) in anhydrous THF (200 mL) was added sodium (0.1 g). The mixture was stirred until Na disappeared and then ieri-butyl acrylate (20.0 mL, 137.79 mmol, 1.0 eq.) was added dropwise. The mixture was stirred overnight and then quenched by HC1 solution (20.0 mL, 1 N) at 0 °C. THF was removed by rotary evaporation, brine (300 mL) was added and the resulting mixture was extracted with EtOAc (3 x 100 mL). The organic layers were washed with brine (3 x 300 mL), dried over anhydrous Na2S04, filtered and concentrated to afford a colorless oil (30.20 g, 79.0percent yield), which was used without further purification. MS ESI m/z [M + H]+ 278.17.
62% With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 20 h; General procedure: To a solution of tetraethylene glycol (20.0 g, 103 mol) in anhydrous THF (54.0 mL) were added NaH (60percent dispersion in mineral oil, 42 mg, 1.05 mmol) and tert-butyl acrylate (5.2 mL, 36.0 mol). The resulting solution was stirred for 20 h at room temperature. The solvent was removed under reduced pressure. The residue was purified by flash column chromatography (petroleum ether/EtOAc=1/1) to afford 16d-1 as a colorless oil (9.3 g, 80percent).
55.5%
Stage #1: With sodium In tetrahydrofuran at 20℃; for 0.2 h; Inert atmosphere
Stage #2: at 20℃; Inert atmosphere
To a solution of 128ml (0.4 mol) tetraethylene glycol and 500ml of dried THF was added 340mg of freshly extruded sodium metal chips. The reaction mixture was stirred under nitrogen at room temperature until all the sodium had dissolved (approximately 2 hours). A portion of tert butyl acrylate (48ml, 0.33mol) was then added and stirred overnight under nitrogen, at room temperature. The reaction was quenched by the addition of 1M HCl and THF removed at reduced pressure. The mixture was then treated with saturated NaCl and extracted with EtOAc. The organic phase was washed with water and dried over anhydrous MgSO4, filtered and concentrated under low pressure to yield a colourless oil (61.3g, 55.5percent).
45%
Stage #1: With sodium hydride In tetrahydrofuran at 20℃; for 0.166667 h;
Stage #2: at 20℃; for 15 h;
First Step
tert-Butyl 3-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]propanoate
2-[2-(2-Hydroxyethoxy)ethoxy]ethanol (2 g, 13.3 mmol) was dissolved in THF (5 mL), and NaH (8 mg, 0.2 mol) was added.
After the mixture was stirred at room temperature for 10 minutes, tert-butyl prop-2-enoate (0.5 g, 3.9 mmol) was slowly added, and the mixture was stirred at room temperature for 15 hours.
The reaction mixture was concentrated, and the resultant residue was purified by column chromatography on silica gel (ethyl acetate) to obtain the target title compound (488 mg, 45percent) as colorless clear oil.
1H-NMR (CDCl3) δ: 3.68-3.65 (4H, m), 3.62-3.55 (10H, m), 2.47 (2H, t, J=6.4 Hz), 1.44 (9H, s).
40% With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; for 72 h; [0072] To 15 grams of polyethene glycol (n=3) was added 0.45 eq of tert-butyl acrylate and 1 molpercent potassium tert-butoxide in THF at 00 C to room temperature for 3 days to yield compound 1. Compound 1 was added to 1.2 eq of methanesulfonyl chloride, 1.2 eq of triethyl amine in THF at 0° C to room temperature for 3 hours. The pH was adjusted to 8 and 1.2 eq of sodium azide was added in water. The reaction was refluxed overnight to yield compound 2. To compound 2 was added 3 eq of triphenyiphosphine in a THF:water ratio of 7:2 at room temperature for 18 hours to afford compound 3.

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