Dimethylformamide → HCID 76282127, compound

Participants

Reaction Steps

N-Chlorosuccinimide (1.82 g, 13.7 mmol) was added in portions to a solution of 4-(2-trifluoromethyl-benzyloxy)-benzaldehyde oxime (which may be prepared as described in Preparation of Intermediate 21; 3.5 g, 11.9 mmol) in DMF (7 mL) at 0° C. The reaction mixture was allowed to warm to room temperature during the addition and then stirred for 2 h at room temperature. The mixture was poured into ice-water and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and evaporated. The residue was dissolved in 50% aqueous tert-butanol (90 mL). Ethyl propiolate (1.2 mL, 11.8 mmol) was added, followed by 1 M sodium ascorbate (1.23 mL, 1.23 mmol) and 0.1 M copper(II) sulfate (120 mL, 12 mmol). KHCO3 (3.75 g, 37.5 mmol) was added and the reaction mixture was stirred at room temperature for 3 h. The solid was filtered off and dissolved in 2 M NH3 in EtOH (15 mL). The resulting mixture was stirred at room temperature overnight. The solvent was evaporated and the residue was purified by chromatography (35-40% EtOAc/hexanes) to give 3-[3-chloro-4-(2-trifluoromethyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide (158 mg, 6%) as a white solid. HRMS Calcd. for C18H13ClF3N2O3 (M+H)+, 397.0562. Found: 397.0558.

Provenance & Evidence