(4-benzyl-3-methylmorpholin-3-yl)methanol

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-benzyl-3-hydroxymethyl-3-methylmorpholine (1 g) in tetrahydrofuran (10 ml) was added dropwise to a suspension of sodium hydride (60% oil suspension; 0.27 g) in tetrahydrofuran (20 ml) at room temperature under nitrogen atmosphere and the whole was stirred at 70° C. for 1 hour. After cooling, methyl iodide (0.34 ml) was added to the mixture and the whole was stirred at 40° C. for 1 hour. After cooling, ethyl acetate and water were added to the mixture and the organic layer was separated, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane (1:4) as an eluent to give 4-benzyl-3-methoxymethyl-3-methylmorpholine (0.77 g) as an oil. After cooling the whole was stirred at 40° C. for 1 hour After cooling the organic layer was separated dried over magnesium sulfate evaporated in vacuo The residue was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane (1:4) as an eluent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium bis(2-methoxyethoxy)aluminum hydride (3.46 M solution in toluene; 42 ml) was added to a solution of 4-benzyl-5-hydroxymethyl-5-methyl-3-morpholinone (10.77 g) in toluene (100 ml) at 0° C. under nitrogen atmosphere and the whole was stirred at room temperature for 1 hour. Ethanol (20 ml) was added to the mixture at 0° C. and the pH of the mixture was adjusted to 12 by 1N sodium hydroxide solution. The organic layer was separated, added 1N hydrochloric acid and the acidic aqueous layer was separated. This procedure was repeated twice and the combined aqueous layer was made alkaline with 4 M sodium hydroxide solution. It was extracted with ethyl acetate, dried over magnesium sulfate and evaporated in vacuo to give 4-benzyl-3-hydroxymethyl-3-methylmorpholine (9.35 g) as an oil. The organic layer was separated added 1N hydrochloric acid the acidic aqueous layer was separated It was extracted with ethyl acetate dried over magnesium sulfate evaporated in vacuo

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-benzyl-3-hydroxymethyl-3-methylmorpholine (1 g) in tetrahydrofuran (10 ml) was added dropwise to a suspension of sodium hydride (60% oil suspension; 0.27 g) in tetrahydrofuran (20 ml) at room temperature under nitrogen atmosphere and the whole was stirred at 70° C. for 1 hour. After cooling, methyl iodide (0.34 ml) was added to the mixture and the whole was stirred at 40° C. for 1 hour. After cooling, ethyl acetate and water were added to the mixture and the organic layer was separated, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane (1:4) as an eluent to give 4-benzyl-3-methoxymethyl-3-methylmorpholine (0.77 g) as an oil. After cooling the whole was stirred at 40° C. for 1 hour After cooling the organic layer was separated dried over magnesium sulfate evaporated in vacuo The residue was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane (1:4) as an eluent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium bis(2-methoxyethoxy)aluminum hydride (3.46 M solution in toluene; 42 ml) was added to a solution of 4-benzyl-5-hydroxymethyl-5-methyl-3-morpholinone (10.77 g) in toluene (100 ml) at 0° C. under nitrogen atmosphere and the whole was stirred at room temperature for 1 hour. Ethanol (20 ml) was added to the mixture at 0° C. and the pH of the mixture was adjusted to 12 by 1N sodium hydroxide solution. The organic layer was separated, added 1N hydrochloric acid and the acidic aqueous layer was separated. This procedure was repeated twice and the combined aqueous layer was made alkaline with 4 M sodium hydroxide solution. It was extracted with ethyl acetate, dried over magnesium sulfate and evaporated in vacuo to give 4-benzyl-3-hydroxymethyl-3-methylmorpholine (9.35 g) as an oil. The organic layer was separated added 1N hydrochloric acid the acidic aqueous layer was separated It was extracted with ethyl acetate dried over magnesium sulfate evaporated in vacuo