Dimethyl Sulfoxide → HCID 59261048, compound

Participants

Reaction Conditions

Reaction Steps

A solution of oxalyl chloride (35.0 μL, 0.402 mmol) in 15 mL of DCM was cooled to −78° C. DMSO (57.0 L, 0.805 mmol) was added drop-wise to the stirring solution. After 5 min 1-((1R,3S)-3-isopropyl-3-{[6-(trifluoromethyl)-2H-1,3-benzoxazin-3(4H)-yl]carbonyl}cyclopentyl)piperidin-4-ol (EXAMPLE 13, TABLE 1, 88 mg) in 5 mL of DCM was added drop-wise over 3 min to the reaction. After stirring for an additional 25 min at −78° C., triethylamine (224.0 μL, 1.609 mmol) in 5 mL of DCM was added drop-wise over 1 min. The reaction mixture was stirred at −78° C. for 10 min before the dry ice/acetone bath was removed. The reaction was allowed to warm to rt and stirred for 1.5 h. The reaction mixture was then diluted with DCM (50 mL) and washed with 1N HCl solution (1×75 mL), sodium bicarbonate solution (1×75 mL), and brine (1×75 mL). The aqueous layers were combined and extracted with dichloromethane (5×100 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification by preparatory TLC (silica gel, 0.4% ammonium hydroxide, 3.6% MeOH, 96% DCM) afforded 1-((1R,3S)-3-isopropyl-3-{[6-(trifluoromethyl)-2H-1,3-benzoxazin-3(4H)-yl]carbonyl}cyclopentyl)piperidin-4-one. ESI-MS calculated for C23H29F3N2O3: 438.48, found 457 (hydrate+H).

Provenance & Evidence