4-Toluenesulfonyl chloride → Triethylene glycol monoethyl ether

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Reaction Steps

p-Toluenesulfonyl chloride (12.583 g, 66.0 mmol) was added to an ice-cooled solution of triethylene glycol monoethyl ether (10.484 ml, 10.694 g, 60.0 mmol) in pyridine (9.7 ml). After being stirred for 3.5 h the reaction was diluted with 10% hydrochloric acid and extracted with ethyl acetate. The organic phase was separated, washed with 10% hydrochloric acid, dried over MgSO4 and concentrated in vacuo to afford sufficiently pure p-toluenesulfonate of triethylene glycol monoethyl ether (19.92 g, 59.9 mmol, 100%) as a reddish liquid. The obtained tosylate (19.5 g, 58.7 mmol) was dissolved in 33% solution of methylamine in methanol (24 ml) and refluxed for 18 h, cooled and concentrated in vacuo. The residue was dissolved in 5% HCl and washed 3 times with dichloromethane. The combined organic solution was back extracted with 5% HCl. All aqueous extracts were combined and mixed with a solution of sodium hydroxide (6 g) in water (14 ml). The resultant solution was extracted with dichloromethane. The combined organic solution was washed with water, dried over MgSO4 and concentrated in vacuo to afford crude 2-(2-(2-ethoxyethoxy)ethoxy)-N-methylethanamine (6.50 g) as a yellowish liquid, which was then used further without additional purification. The crude 2-(2-(2-ethoxyethoxy)ethoxy)-N-methylethanamine (0.426 g, 1.86 mmol) was added to suspension of compound 1 (1.07 g, 0.928 mmol) in a mixture of triethylamine (1.293 ml, 0.939 g, 9.28 mmol) and DMF (5 ml). The reaction mixture was stirred overnight and diluted with ether. The obtained solid was collected by filtration, washed with ether, and dried in vacuo to afford the desired compound 2c (0.93 g, 0.80 mmol, 86%) as a pale solid. The crude material was used in the next step without further purification.

Provenance & Evidence