| 72.8% |
|
1.122 g of tBuOK (potassium tert-butoxide) was dissolved in 6.5 ml of dry THF (tetrahydrofuran)2.12g of diethylene glycol was added under the protection of ice-water outer bath under argon, the reaction was stirred for 30 minutes, then 1.18g of bromopropyne was added dropwise,The reaction was complete after dropping 1 hour ice water bath, the reaction was carried out at room temperature for 12 hours, the reaction was stopped after diatomaceous earth filter layer, the filtrate evaporated to give a yellow oil, 300-400 mesh silica gel medium pressure separation,The mobile phase of petroleum ether: ethyl acetate = 4: 1, the product fractions were collected and evaporated to give the product 0.976g pale yellow oily product, yield 72.8%. |
| 65% |
|
General procedure: Sodium hydride (1.5 eq.) was added under a nitrogen atmosphere to a cooled (0 C) solution ofpolyethylene glycol 9 (1 eq.) in anhydrous DMF followed by a solution of propargyl bromide intoluene (80% wt, 3 eq.). The reaction mixture was stirred at room temperature for 2 days. It was thenconcentrated in vacuo to give an oil, which was purified by column chromatography (hexane/EtOAc). |
| 58.3% |
|
2,2-oxydiethanol (168 mmol) in THF (100 ml) was added dropwise to a solution of sodium hydride (42mmol) in THF (80 ml) at 0C during 30 minutes. The solution was stirred for 2 hours at room temperature. 3-bromoprop-1-yne (42 mmol) was added and the solution was refluxed overnight, followed by addition of water (80 ml). Solvent was evaporated and extracted with EtOAc (4x lOOmI). The combined organic layers were washed with brine, dried over anhydrous Na2504, filtered and concentrated in vacuo. The obtained mixture was purified with flash chromatography (100% Heptaneto 40% EtOAc in Heptane)Yield: 58.3 %, MS (ESI) m/z 167 [M+Na] +1H-NMR (ODd3, 400 MHz) 6 2.44 (t, J=2.4 Hz, 1H), 3.62 (t, J=4.4 Hz, 2H), 3.69-3.77 (m, 6H), 4.22 (d, J=2.4Hz, 2H) |
| 53% |
|
General procedure: In an oven dried REF, di or tetra ethylene glycol (DEG or TEG) (1.0 eq) was dissolved with stirring in TRF. Sodium hydride (NaR) (1.0 eq) was added to the flask in small portions at 0 C. After 1 hour, propargyl bromide (0.7 eq) was added dropwise, maintaining the reaction at the same temperature. Then reaction was stirred for 12 hours at RT. Upon completion, excess NaR was quenched with dropwise addition of water. Resulting reaction mixture was extracted in DCM thrice. Combined organic layer was dried over Na2504 and concentrated under vacuum to get crude product, which was purified using silica gel column chromatography using MeORDCM as eluent. The compound 9a was prepared by general procedure 4.1.1, starting from diethylene glycol (1.2 g, 11 mmol), NaH (0.034 g, 1.4 mmol), propargyl bromide (1.3 g, 10 mmol) in THF. The product was obtained as a pale yellow liquid (2.1 g, 15 mmol, 53%) after purification by silica gel column chromatography using MeOH/DCM as eluent, R1=0. 36 in 5% MeOH/DCM. ?H NMR (400 MHz, CDC13): oH4.17 (d, J=2.4 Hz, 2H), 3.70-3.63 (m, 7H), 3.57 (t, J=4.4 Hz,3H), 2.43 (t, J=2.4 Hz, 1H).10392] ?3C NMR (100 MHz, CDC13): O 79.47, 77.16,74.83, 72.58, 70.17, 69.12, 61.65, 58.41. HRMS (M+H): 145.12.Mol. formula: C7H,203Mol. Weight: 144.07Physical appearance: pale yellow liquidYield: 53% |
| 51% |
|
Into a round-bottom flask (RBF) charged with argon and cooled to 0 C, 95 % NaH (1.64 g, 65 mmol) was suspended in anhydrous THF. Di(ethylene)glycol (9.5 mL, 100 mmol) was added dropwise. After 30 min of stirring at 0 oC, propargyl bromide (5.5 mL, 50 mmol, 80 % in toluene) was added slowly. The reaction was kept at 0 oC for another 2 h, then allowed to warm to RT overnight. The reaction was slowly quenched with water (30 mL) and the compound was extracted into CH2Cl2 (3 x 50 mL). The organic portions were combined and washed with H2O (1 x 30 mL), dried over Na2SO4, and concentrated in vacuo. Flash chromatography on a silica column (3:2 ethyl acetate:hexanes ) afforded alkyne 7 (3.66 g, 51 %) as a yellow oil. 1H NMR (CDCl3): delta 2.43 (t, 1H, J = 2.4Hz); 2.84-2.88 (br s, 1H), 3.58 (dt, 2H, J = 4.6Hz, 5.3Hz); 3.76-3.63 (m, 6H); 4.18 (d, 2H, J = 2.8Hz). 13C NMR (CDCl3): delta 58.5 [CH2]; 61.8 [CH2]; 69.2 [CH2]; 70.3 [CH2]; 72.7 [CH2]; 74.9 [CH]; 79.6 [C]. HRMS (ESI+) calcd. for C7H12O3Na [M++Na]: 167.0684. Found: 167.0680. |
| 50% |
|
To a mixture of t-BuOK (4.76 g, 42.5 mmol) in THF (120 mL) was added 2-(2-hydroxyethoxy)ethanol (8.92 g, 84.0 mmol, CAS111-46-4) at 0 C. The reaction mixture was stirred at rt for 30 minutes and then 3-bromoprop-1-yne (5 g, 42.0 mmol) in THF (25 mL) was added dropwise. The reaction mixture was stirred at rt for 12 hours. On completion, the mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography (SiO2) to give the title compound (3 g, 50% yield) as yellow oil. 1H NMR (400 MHz, CDCl3) delta 4.20 (d, J=2.4 Hz, 2H), 3.76-3.65 (m, 6H), 3.63-3.56 (m, 2H), 2.44 (t, J=2.4 Hz, 1H), 2.41 (s, 1H). |
| 45.3% |
|
46 mL of diethylene glycol (Compound 43) was dissolved in 100 mL of dry tetrahydrofuran, cooled to 0 C, and 5.5 g of sodium hydride was added in small batches. After the addition was completed, the reaction was continued at this temperature for 2 hours. Weigh 10g of 3-bromopropyne in 30mL of dry tetrahydrofuran, and slowly add it to the above reaction. After completion, react at room temperature overnight. 20 mL of water was added to the reaction system, tetrahydrofuran was concentrated, extracted with ethyl acetate (50 mL × 3), and the organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 5.53 g of compound 44 by column chromatography with a yield of 45.3% |
| 38% |
|
Weigh 64mg (1.2eq) of potassium tert-butoxide dissolved in dry THF solution, add diethylene glycol 200mg (1.0eq) under N2 environment, stir under ice salt bath for 30min, then add one dropwise with a constant pressure dropping funnel bromopropyne (1.5eq) solution diluted in THF, stirred overnight at room temperature, the reaction was fully completed, and finally the insoluble matter was sucked off with a suction filter funnel, the THF was swirled at low temperature, concentrated under reduced pressure and purified by column chromatography to obtain a yellow liquid 7. The yield is 38%. |
| 30% |
|
To a stirred suspension of potassium ie f-butoxide (1 .06 g, 9.42 mmol) in THF (300 mL) cooled to 0C in an ice-bath was added a solution of 2,2'-oxydiethanol (4.60 g, 78.0 mmol) in THF (10 mL). The mixture was stirred at 0C for 30 min and was then allowed to warm to RT and was treated dropwise with propargyl bromide (1.68 mL of an 80% solution in toluene, 1 1 .30 mmol). The reaction mixture was stirred at RT for 16 hr and diluted with brine and water (5:1 , 50 mL) and was extracted with EtOAc (3 x 500 mL). The combined organic extracts were dried, filtered and evaporated in vacuo. The residue was purified by flash column chromatography, eluting with 25 to 60% EtOAc in heptane, to afford the title compound (10) (410 mg, 30%) as a yellow oil: 1H NMR (250 MHz, CDCI3) delta: 2.22 (1 H, s), 2.45 (1 H, t), 3.58-3.66 (2H, m), 3.67-3.79 (6H, m), 4.22 (2H, d). |
| 30% |
|
2-(2-(Prop-2-ynyloxy)ethoxy)ethanol (10) To a stirred suspension of potassium tert-butoxide (1.06 g, 9.42 mmol) in THF (300 mL) cooled to 0 C. in an ice-bath was added a solution of 2,2'-oxydiethanol (4.60 g, 78.0 mmol) in THF (10 mL). The mixture was stirred at 0 C. for 30 min and was then allowed to warm to RT and was treated dropwise with propargyl bromide (1.68 mL of an 80% solution in toluene, 11.30 mmol). The reaction mixture was stirred at RT for 16 hr and diluted with brine and water (5:1, 50 mL) and was extracted with EtOAc (3*500 mL). The combined organic extracts were dried, filtered and evaporated in vacuo. The residue was purified by flash column chromatography, eluting with 25 to 60% EtOAc in heptane, to afford the title compound (10) (410 mg, 30%) as a yellow oil: 1H NMR (250 MHz, CDCl3) delta: 2.22 (1H, s), 2.45 (1H, t), 3.58-3.66 (2H, m), 3.67-3.79 (6H, m), 4.22 (2H, d). |
|
|
Weigh 64mg (1.2eq) of potassium tert-butoxide and dissolve it in a dry THF solution. Add 200mg (1eq) of polyethylene glycol chains of different lengths under N2 environment, and stir for 30min in an ice-salt bath. Subsequently, a THF-diluted bromopropyne solution was added dropwise with a constant-pressure dropping funnel, and the mixture was stirred at room temperature overnight. Finally, the insoluble matter was removed with a suction filtration funnel, the THF was removed at low temperature, concentrated under reduced pressure, and purified by column chromatography to obtain a yellow liquid 6 with a yield of 38%. |
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