Methylamine → 4-Methylaminomethyl-2-phenyl-1,3-dioxane

Participants

Reaction Steps

To a solution of 4-hydroxymethyl-2-phenyl-1,3-dioxane (0.80 g, 4.12 mmol) in dichloromethane (20 mL) was added diisopropylethylamine (1.702 ml, 10.30 mmol) and the solution was cooled in an ice bath. Methanesulfonyl chloride (0.414 ml, 5.35 mmol) was added and the solution was allowed to warm to RT. After 1 h, it was washed with 2M aq HCl, saturated aq NaHCO3, dried and concentrated to a syrup (1.15 g). A solution of (0.9 g, 3.30 mmol) of this material in DMSO (8 mL) containing 40% aq methylamine (2.85 ml, 33.0 mmol) was stoppered and heated at ˜75-80° C. for 24 h. The solution was cooled, chloroform was added and washed twice with water, dried and concentrated. Chromatography afforded title compound (0.465 g, 2.24 mmol, 68%) as a syrup. 1H NMR (CDCl3) δ 7.50-7.47 (2H, m), 7.39-7.30 (3H, m), 5.52 (1H, s), 4.31-4.25 (1H, m), 4.09-3.93 (2H, m), 2.80 (1H, dd, J=12.3, 8.0 Hz), 2.67 (1H, dd, J=12.3, 3.4 Hz), 2.45 (3H, s), 1.96-1.83 (2H, m), 1.49 (1H, dd, J=13.2, 1.2 Hz); 13C NMR δ 139.0, 129.2, 128.6, 126.5, 101.6, 76.8, 67.2, 57.0, 36.8, 29.5.

Provenance & Evidence