Morpholine → Methyl 4-(morpholin-4-ylmethyl)benzoate

Participants

Reaction Conditions

Reaction Steps

A 2 L, three-neck flask fitted with a mechanical stirrer, addition funnel, and thermocouple probe was charged with 4-formyl-benzoic acid methyl ester (50.0 g, 0.31 mol, 1.0 eq) and 1,2-dichloroethane (700 mL). The resulting mixture was cooled to 10° C. Morpholine (53 mL, 0.61 mol, 2.0 eq) was then added dropwise over 10 min. After 5 min, sodium triacetoxyborohydride (90 g, 0.43 mol, 1.4 eq) was added in portions over 5 min. After stirring 30 min, the reaction mixture was warmed to room temperature. At this point, a slow and steady temperature increase was observed, and a water bath was used to keep the temperature of the reaction mixture below 25° C. The reaction mixture was stirred for 22 hrs at room temperature. Water/ice (100 mL) was added to the reaction and the reaction mixture was stirred for 15 min. NaOH solution (1.0 M in water, 400 mL) was added in several portions, followed by the addition of water (250 mL). The resulting mixture was stirred for 45 min. The layers were separated, and the aqueous layer was extracted with dichloromethane (150 mL). The combined organic layer was washed with brine (150 mL) and then dried over Na2SO4. The solvent was removed in vacuo to yield the title compound as a pale yellow, viscous oil.

Provenance & Evidence