Morpholine → HCID 70564713, compound

Participants

Reaction Steps

To an ice cold, stirred solution of 7.16 g (0.02 mole) of compound 1 (Scheme 3) in 40 ml of methylene chloride were added dropwise 9.70 g (0.048 mole) of bromoacetyl bromide dissolved in 10 ml of methylene chloride followed by a solution of 4.84 g (0.048 mole) of triethylamine in 10 ml of methylene chloride. The temperature was maintained below 8° C. during both additions. The reaction mixture was stirred in an ice bath for 1.5 hours and then at room temperature for 4 hours. Most of the solvent was removed under a rapid stream of nitrogen in a water bath held at 35°-40° C. The residue was taken up in 40 ml of dry dimethylformamide cooled in ice and treated dropwise with 8.71 g (0.10 mole) of morpholine, keeping the reaction temperature below 15° C. After being stirred at room temperature overnight, the reaction mixture was poured into water, insoluble material was taken up in methylene chloride, washed with water and concentrated to dryness. The residue (11.3 g) was taken up in 100 ml of methanol, cooled in ice, treated with 10 ml of 45 percent potassium hydroxide solution and stirred at room temperature under a nitrogen atmosphere for 2 hours. The solution was cooled in ice and neutralized to pH 9 (approximate) using 6 N hydrochloric acid and dry ice. The precipitate (about 11 g) was collected at the filter and shaken with a mixture of water and methylene chloride until solution was complete. The organic layer was separated, washed with water and concentrated to dryness. The crystalline residue (5.0 g), m.p. 205°-215° C., was recrystallized from dimethoxyethane to give 2.76 g of the above-titled compound, m.p. 217°-219° C.

Provenance & Evidence