4-benzyl-2,2-dimethylmorpholine synthesis

Yield:84761-04-6 54%

Reaction Conditions:

Stage #1: 2-(benzyl(2-methylallyl)amino)ethanolwith mercury(II) diacetate in tetrahydrofuran;water; for 3 h;
Stage #2: with sodium hydroxide in tetrahydrofuran;water; for 19 h;

Steps:

151

Add 2-[benzyl-(2-methyl-allyl)-amino]-ethanol (13.0 g, 63.2 mmol) to a slurry of mercury (H) acetate (20.7 g, 65.0 mmol) in water (45 mL) and THF (45 mL). After 3 h, treat the mixture with NaOH (25 mL, 2.5 M aqueous, 125 mmol) followed by NaBH₄ (2.72 g, 71.9 mmol). After 19 h, decant the mixture away from the metallic mercury and add to a separatory funnel with fert-butyl methyl ether (250 mL). Separate the organic solution, wash with water (250 mL), filter through a silica plug, and concentrate. Purify the residue by flash chromatography using a gradient from 5% to 10% tert-butyl methyl ether in CH₂Cl₂. Collect and concentrate the fractions containing product then dissolve the residue in hexanes (100 mL). Filter the solution through Celite to remove metallic mercury and then concentrate the filtrate to give the title compound (7.01g, 54%) as a colorless liquid. ¹H NMR (DMSO-d6, 400 MHz) δ 7.20-7.40 (5H, m), 3.60 (2H, m), 3.42 (2H, s), 2.29 (2H. m), 2.10 (2H, s), 1.14 (6H, s).

References:

WO2006/66174,2006,A1 Location in patent:Page/Page column 132