2-[2-(BENZYLOXY)ETHOXY]ETHANOL

Diethylene Glycol Monobenzyl Ether is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].

General procedure: Dioxane (15 mL), alkyl halide (25 mmol), and tetrabutylammonium bromide (0.4 g, 1.2 mmol) were added to a solution of KOH (1.6 g, 27.5 mmol) in glycol (75—125 mmol). After stirring at 100—105 °C for 5—10 h, the reaction mixture was diluted with CHCl3 (15 mL) and water (10 mL). The organic layer was separated, washed with water (3×20 mL), dried with Na2SO4, and evaporated in vacuo, and the residue was distilled using Vigreux column. For each particular case, the ratio of the starting reagents, yields, physicochemical parameters, and 1H NMR spectral data for monoalkyl ethers 8a—e are givenin Table 6.2-(2-methoxyethoxy)ethanol (2A) (21.2 g, 0.2 mol) and cesium carbonate (8.55 g, 0.05 mol) were dissolved in N, N-dimethylformamide (50 mL) benzyl bromide (27.7 g, 0.085 mol) was added and stirred at room temperature for 3 days. The reaction solution was extracted with water (300 mL) and extracted with ethyl acetate (100 mL x 2). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography Ether / ethyl acetate (v / v) = 1: 0-5: 1) to give the title product 2- (2-benzyloxyethoxy) ethanol (2B) as a pale yellow oil (4.0 g, yield 40 percent).A mixture of 2- (2-methoxyethoxy) ethanol(2A) (21.2 g, 0.2 mol) andCesium carbonate (8.55 g, 0.05 mol) was dissolved in N, N-dimethylformamide (50 mL), Benzyl bromide (27.7 g, 0.085 mol) was added and stirred at room temperature for 3 daysThe The reaction solution was added with water (300 mL) and extracted with ethyl acetate (100 mL x 2)The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography(Petroleum ether / ethyl acetate (v / v) = 1: 0 to 5: 1) to give the title product2- (2-benzyloxyethoxy) ethanol (2B) as a pale yellow oil(4.0 g, yield 40percent).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.

Molecular Weight:196.24
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:7
Exact Mass:196.109944368
Monoisotopic Mass:196.109944368
Topological Polar Surface Area:38.7
Heavy Atom Count:14
Complexity:122
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes