Bis(2-oxo-3-oxazolidinyl)phosphinic chloride → (3S)-ethyl 1-(2-hydroxy-2-(4-(5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate

Participants

Reaction Steps

To a mixture of 3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazole-5-carboxylic acid, Int-IV (45 mg, 0.174 mmol), (3S)-ethyl 1-(2-hydroxy-2-(4-((E)-N′-hydroxycarbamimidoyl)phenyl)ethyl)piperidine-3-carboxylate (70 mg, 0.209 mmol), and BOP-Cl (53 mg, 0.208 mmol) in DMF (5 mL) was added TEA (0.073 mL, 0.523 mmol). The reaction mixture was stirred at room temperature for 2 hr then TBAF (0.174 mL, 0.174 mmol) was added. Next, the reaction mixture was stirred for 3 days. The reaction mixture was diluted with ethyl acetate and washed with saturated NaCl. The organic layer was dried with MgSO4, filtered, and concentrated. The crude residue was purified by a silica gel cartridge using an EtOAc/hexanes gradient to yield 37 mg of (3S)-ethyl 1-(2-hydroxy-2-(4-(5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate.

Provenance & Evidence