Triethylamine → Ethyl 3-phenyl-4-propylisoxazole-5-carboxylate

Participants

Reaction Steps

To a solution of (Z)-N-hydroxybenzimidoyl chloride (770 mg, 4.95 mmol) and ethyl 2-bromohex-2-enoate (1.09 g, 4.95 mmol) in DCM (15 mL) was added triethylamine (2.07 mL, 14.85 mmol) over 5 minutes. After ˜50% of the addition was complete, a precipitate formed. Stirring was continued for 24 hr at rt. The reaction mixture was partitioned between Et2O (100 ml) and water (100 ml). The organic layer was washed with brine (100 ml), dried (MgSO4) and concentrated to afford a yellow oil. This oil was chromatographed on a 5×15 cm silica gel column, eluting with a 0-8% EtOAc/Hex gradient. The product containing fractions were concentrated to afford 343 mg of a waxy, white solid. This material was triturated with heptane. The solid contained no product. The mother liquor was concentrated to afford a partially purified semisolid residue. The portion of the residue that dissolved in ˜3 ml of hexane was chromatographed on a 12 gm Isco silica gel cartridge, eluting with a 0-1% EtOAc/Hex gradient. Fractions containing the product were concentrated to afford ethyl 3-phenyl-4-propylisoxazole-5-carboxylate (34 mg, 0.131 mmol, 2.65% yield) as a colorless oil. HPLC retention time=1.91 minutes (PHENOMENEX® Luna 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1% TFA over a 2 minute gradient. MS: (M+H)=260.23. 1H NMR (500 MHz, chloroform-d) δ ppm 0.90 (t, J=7.4 Hz, 3H), 1.45 (t, J=7.2 Hz, 3H), 1.53 (m, 2H), 2.80 (m, 2H), 4.46 (q, J=7.2 Hz, 2H), 7.45 (m, 1H), 7.50 (m, 2H), 7.59 (m, 2H).

Provenance & Evidence