Trichloroisocyanuric Acid → 4-(tert-Butoxycarbonyl)morpholine-3-carboxylic acid

Participants

Reaction Steps

Saturated aqueous NaHCO3 (15 mL) was added to a stirred solution of tert-butyl 3-(hydroxymethyl)morpholine-4-carboxylate (1.09 g, 5.0 mmol) (Organic and Bio-Organic Chemistry (1972-1999); (1985); 2577-2580, WO 2006/114606 and US 2010/210640) in acetone (50 mL) at 0° C. Solid NaBr (0.1 g, 1 mmol) and TEMPO (0.015 g, 0.1 mmol) were added. Trichloroisocyanuric acid (2.32 g, 10.0 mmol) was then added for 20 min at 0° C. After addition, the reaction mixture was allowed to room temperature (RT) and further maintained overnight. 2-Propanol (3 mL) was added and the resulting solution was stirred at RT for 30 min, filtered through a pad of Celite, concentrated under vacuum, and treated with saturated aqueous Na2CO3 solution (15 mL) The aqueous solution was extracted with EtOAc (5 mL), acidified with 6N HCl and extracted with EtOAc (5×10 mL). The combined organic layers were dried over Na2SO4 and the solvent was concentrated to give title compound as a white solid (760 mg). (M−H)−229.9.

Provenance & Evidence