1,2-Dichloroethane → HCID 58537219, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(difluoromethyl)-3-phenylisoxazole-5-carboxylic acid (28 mg, 0.117 mmol), (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate, Int.1, (35.7 mg, 0.117 mmol), HOBT (28.7 mg, 0.187 mmol), EDC (52.7 mg, 0.275 mmol) and diisopropylethylamine (82 μL, 0.468 mmol) in DMF was stirred at rt for 3 hr and at 55° C. for 18 hr. The reaction mixture was partitioned between EtOAc (30 ml) and saturated sodium bicarbonate solution (30 ml). The organic layer was washed with water (2×30 ml) and brine (30 ml). After drying (MgSO4) and filtration, the organic layer was concentrated to a yellow oil that was chromatographed on a 4 gm Isco silica gel cartridge, eluting with a 0-50% EtOAc/Hex gradient. The essentially pure fractions containing the product were concentrated to afford tert-butyl 1-(4-(5-(4-(difluoromethyl)-3-phenylisoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (23 mg, 0.045 mmol, 38.6% yield) as a white solid. HPLC retention time=1.80 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)=509.14.

Provenance & Evidence