Dimethylformamide → 4-(4-Bromo-thiazol-2-yl)-cis-2,6-dimethyl-morpholine

Participants

Reaction Conditions

Reaction Steps

A 1 L flask equipped with a mechanical stirrer and a thermometer was charged with 2,4-dibromothiazole (60 g, 0.247 mol) and DMF (480 mL). After dissolution, cis-2,6-dimethylmorpholine (33.65 mL, 0.272 mol) and DIPEA (61.23 mL, 0.37 mol) were added under a stream of nitrogen. The reaction mixture was heated to 70° C. under nitrogen and stirred overnight. The reaction mixture was cooled to 10° C. in an ice/water bath. Then water (1 L) was added dropwise in a temperature range of 10-20° C. A slightly exothermic reaction was observed, with formation of an off-white precipitate. After the addition, the reaction mixture was stirred for 30 min. The precipitate was then filtered and washed with water (50 ml). The collected solid was dried in a vacuum oven at 50° C., yielding 52.8 g (77%) of Intermediate 1 as an off-white solid.

Provenance & Evidence