(2R)-2-(Methoxymethyl)morpholine synthesis

107-35-7

64491-70-9

157791-21-4

General procedure for the synthesis of R-2-methoxymethylmorpholine: 1. a solution of (R)-(-)-epoxypropyl methyl ether (0.800 g, 10.66 mmol) in methanol (11 mL) was slowly added dropwise to a mixture of 2-aminoethanesulfonic acid (6.440 g, 53.3 mmol) dissolved in 40% aqueous sodium hydroxide (11 mL) at a reaction temperature of 50 °C. the reaction was carried out by stirring the reaction mixture at 50 °C. 2. After stirring the reaction mixture for 75 minutes, 40% aqueous sodium hydroxide solution (19 mL) was added and stirring was continued at 50 °C for 20 hours. 3. After completion of the reaction, the solution was cooled to room temperature and diluted with deionized water (76 mL). 4. The aqueous phase was extracted with ethyl acetate (3 x 75 mL) and the organic phase was combined. 5. The organic phase was dried over anhydrous sodium sulfate (Na2SO4) and the solvent was subsequently removed under reduced pressure. 6. The crude product was purified by fast column chromatography on silica gel with ethyl acetate-hexane (2:8) as eluent to afford R-2-methoxymethylmorpholine as a colorless oil (0.121 g, 10% yield). 7. The structure of the product was determined by 1H NMR chromatography. 7. The structure of the product was confirmed by 1H NMR (500 MHz, (CD3)2CO): δ 2.47 (1H, dd, J = 10.4, 1.9 Hz), 2.70-2.72 (1H, m), 2.84 (1H, dd, J = 11.9, 2.2 Hz), 3.22-3.25 (2H, m), 3.27 (3H, s), 3.29-3.34 (3H, s), 3.30-3.31 (3H, s), 3.31-3.31 (3H, s), 3.31-3.31 (3H, s), 3.31-3.31 (3H, s). 3.29-3.34 (4H, m), 3.45-3.53 (2H, m), 3.73 (1H, dt, J = 11.0, 2.5 Hz).