Triethylamine → HCID 90202458, compound

Participants

Reaction Conditions

Reaction Steps

4-(3-Fluoro-benzyloxy)-benzaldehyde oxime (which may be prepared as described in Preparation of Intermediate 3; 2 g, 8.2 mmol) was dissolved in DMF (4.8 mL) and the solution was cooled to 0° C. in an ice-water bath. N-Chlorosuccinimide (1.09 g, 8.2 mmol) was added slowly. The reaction mixture was stirred at 0° C. for 30 min, allowed to warm to room temperature and stirred at room temperature for 1 h. The reaction mixture was poured into ice-water (125 mL) and the resulting suspension was extracted with EtOAc (200 mL). The organic extract was dried over Na2SO4, filtered, and evaporated. The residue was dissolved in Et2O (20 mL). A mixture of ethyl propiolate (1.1 mL, 10.9 mmol) and triethylamine (1.5 mL) in Et2O (20 mL) was added dropwise, and the mixture was stirred at room temperature for 9 days. Silica gel was added and the solvent was evaporated. The resulting mixture was purified by chromatography (5-15% EtOAc/hexane) to give 3-[4-(3-fluoro-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid ethyl ester (160 mg, 6%) as a white crystalline solid, which contained some of the undesired 4-carboxylic acid ethyl ester regioisomer.

Provenance & Evidence