Chloromethyl Methyl Ether → (3S)-3-(Methoxymethoxy)pyrrolidine

Participants

Reaction Steps

To a stirred solution of N-benzyl-3-(S)-hydroxypyrrolidine (4.785 g, 27 mmol) in THF (50 ml) was added sodium hydride (60% oil suspension, 1.12 g, 28 mmol) by portions under nitrogen at room temperature. The suspension mixture was then refluxed for 1 h. To this reaction mixture was added chloromethyl methyl ether (2.3 ml, 30 mmol) and refluxing was continued for 13 h. After cooling down to room temperature, water (10 ml) was added to the reaction mixture to give a solution mixture, which was basified with 1N NaOH aqueous solution, extracted with ethyl acetate (30 ml×3), and dried (Na2SO4). Evaporation of the solvent gave 6.33 g of brown oil, which was purified by column chromatography (silica gel: 150 g, CH2Cl2 /MeOH: 20/1 as eluent) to afford 5.09 g (85%) of clear brown oil. A suspension mixture of this oil (5.09 g, 23 mmol) and Pearlman's catalyst (2.00 g) in MeOH (100 ml) was stirred under hydrogen atmosphere at room temperature for 15 h. After removal of the catalyst by Celite filtration, the filtrate was concentrated to give an oil and water mixture, which was dried in vacuo to afford 2.76 g (91.4%) of orange color oil.

Provenance & Evidence