Mes-PEG5- THP synthesis

Yield:145927-73-7 21.9%

Reaction Conditions:

with pyridinium p-toluenesulfonate in dichloromethane at 20; for 3 h;

Steps:

1 2-(2-{2-[2-(2-methanesulfonyloxyethoxy)ethoxy]ethoxy}ethoxy)tetrahydro-2H-pyran (2)

The tetraethylene glycol (8.90mL, 0.052mmol) and triethylamine (16.70mL, 0.12mol) was dissolved in 50mL of methylene chloride was slowly dropped into an ice-water bath cooling methanesulfonyl chloride (8.05mL, 0.104mol), dropwise stirred at room temperature after 4h.The solvent was evaporated under reduced pressure, followed with water, 1N HCl, saturated NaHCO after the residue was diluted with ethyl acetate₃And the solution was washed with saturated brine, dried over anhydrous Na₂SO₄After drying the solvent was evaporated, and concentrated under reduced pressure to give 2- {2- [2- (2-methanesulfonyloxy-ethoxy) ethoxy] ethoxy} ethanol (8.70g, 62.1%), the product was used without further purification in the next reaction.The above 2- {2- [2- (2-methanesulfonyloxy-ethoxy) ethoxy] ethoxy} ethanol (8.70g, 31.97mmol) was dissolved in dry dichloromethane (100mL), the was added pyridinium p-toluenesulfonate (PPTS, 0.80g, 3.20mmol) was added dropwise dihydropyran (DHP, 4.38mL, 47.96mmol), stirred for 3 hours at room temperature.After completion of the reaction, the crude product was diluted with ethyl acetate, washed with water three times, brine, dried over anhydrous Na₂SO₄dry.The solvent was distilled off, the resulting residue was purified by flash silica gel column chromatography (petroleum ether / ethyl acetate: 50/1, V / V) give a clear oil (2.50g, 21.9%).

References:

CN103819486,2016,B Location in patent:Paragraph 0041-0044