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

Yield: 10%

Reaction Conditions:

with sodium hydroxide in methanol at 50; for 21.25 h;

Steps:

15-1-A
Synthesis 15-1 -A; (f?)-2-(Methoxymethyl)morpholine; A solution of (R)-(~) glycidylmethylether (0.800 g, 10.66 mmol) in methanol (11 mL) was added dropwise to a solution of 2-aminoethanesulfonic acid (6.440 g, 53.3 mmol) in 40% aqueous sodium hydroxide (11 mL) at 5O⁰C. After stirring for 75 minutes, further 40% aqueous sodium hydroxide (19 mL) was added and the reaction mixture was stirred for 20 hours at 5O⁰C. The solution was cooled to room temperature and diluted with water (76 mL). The aqueous phase was extracted with ethyl acetate (3 x 75 mL). The combined organic phases were dried (Na₂SO₄). The solvent was removed in vacuo and the crude mixture was purified by flash chromatography on silica, eluting with ethyl acetate-hexane (2:8), to give the title compound as a colourless oil (0.121 g, 10%).¹H NMR (500 MHz₁ (CD₃)₂CO) 2.47 (1 H, dd, J = 10.4, 1.9), 2.70-2.72 (1H, m), 2.84 (1 H₁ dd, J = 11.9, 2.2), 3.22-3.25 (2H, m), 3.27 (3H, s), 3.29-3.34 (4H, m), 3.45-3.53 (2H, m), 3.73 (1H, dt, J = 11.0, 2.5).

References:

CANCER RESEARCH TECHNOLOGY LIMITED WO2008/75007, 2008, A1 Location in patent:Page/Page column 106-107