Triethylamine → HCID 12056915, compound

Participants

Reaction Conditions

Reaction Steps

A 50 mL round bottom flask equipped with a stir bar, thermocouple, and a reflux condenser was charged with (2R)-1-amino-1-(4-bromophenyl)propan-2-ol (480 mg, 2.09 mmol), triethylamine (222 mg, 0.3 mL, 2.19 mmol) and THF (10 mL). The reaction mixture was cooled to 10° C. 2,6-Difluorobenzoyl chloride (387 mg, 2.1 mmol) was added to the THF solution keeping the temperature <30° C. The reaction mixture was stirred at 25-30° C. for 2 hours. Dichloromethane (40 mL) and water (60 mL)were added and the phases were separated. The aqueous layer was extracted with dichloromethane (2×20 mL). The combined organic extracts were washed with aq. 0.5 N HCl (50 mL) and brine (50 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to give crude amide, which was placed in a 50 mL round bottom flask equipped with a stir bar, thermocouple, and a reflux condenser. The residue was dissolved in dichloromethane (25 mL), and the reaction mixture was cooled to −78° C. (Diethylamino)sulfur trifluoride (337 mg, 0.28 mL, 2.09 mmol) was added to the dichloromethane solution keeping the temperature −70° C. The reaction mixture was allowed to warm to 25° C. while stirring over 16 h. The reaction mixture was poured into 50 g ice containing conc. ammonium hydroxide (5 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic extracts were washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to give crude product as a mixture of diastereomers. Column chromatography gave two products (270 mg of (4S,5S) as an oil and 171 mg of (4S,5R) as an oil, 60% overall yield for the combined isomers over the two steps).

Provenance & Evidence