Dimethylformamide → Methyl 2-[2-(morpholin-4-ylmethyl)-5-ethylphenoxy]propanoate

Participants

Reaction Conditions

Reaction Steps

To a one liter round bottom flask equipped with a mechanical stirrer and a thermometer was added 157.13 grams (1.14 moles--1.3 equiv.) of potassium carbonate, followed by 215.27 grams (0.875 mole--1.0 equiv.) of 89.9% pure 2-(morpholin-4-ylmethyl)-5-ethylphenol, and 230 mL (%Wt/Vol. Phenol to Solvent--93.6%) of N,N-dimethylformamide. The mixture was vigorously stirred and heated to 110° C., and then 139.3 grams (1.14 moles--1.3 equiv.) of methyl 2-chloropropanoate was added during a one hour period. Upon completion of addition, the reaction mixture was analyzed by GC, which indicated the reaction was incomplete. The reaction mixture was heated at 110° C. for seven hours. After this time, the reaction mixture was again analyzed by GC, which indicated the reaction was complete. The reaction mixture was filtered, and the orange filtrate was kept under a nitrogen atmosphere for about 48 hours. After this time, the filtrate was concentrated under vacuum at 90° C. and 10 mm of mercury to yield a red, brown liquid. The liquid was taken up in 200 mL of toluene, and the resulting solution was washed with two 500 mL portions of an aqueous saturated sodium chloride solution. The organic layer was separated from the aqueous layer, dried with magnesium sulfate, and filtered. The filtrate was concentrated under vacuum at 90° C. and 10 mm of mercury, yielding 252.7 grams of 83.6% pure methyl 2-[2-(morpholin-4-ylmethyl)-5-ethylphenoxy]propanoate (78.6% yield). The NMR spectrum was consistent with the proposed structure.

Provenance & Evidence