3-azetidinecarboxylic Acid → HCID 46846917, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2-methyl-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde (0.050 g, 0.125 mmol) and azetidine-3-carboxylic acid (0.015 g, 0.150 mmol) in methanol (0.5 mL) and dichloroethane (0.5 mL) at room temperature was added 3 drops of acetic acid via a pasteur pipette. The reaction mixture was heated at 60° C. for 1 h. The reaction was cooled to room temperature, sodium cyanoborohydride (9.59 mg, 0.150 mmol) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane, washed with water, washed with brine, and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded a white solid which was triturated with methanol with sonication and filtered. The resulting white solid was purified by flash silica gel chromatography using a mixture of methanol, dichloromethane, and ammonium hydroxide (10:90:0-20:80:1) to give 1-(2-methyl-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid (0.032 g, 0.065 mmol, 52% yield) as a white solid. The compound had an HPLC ret. time=2.82 min.−Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=485.2. 1H NMR (500 MHz, DMSO-d6) δ ppm 2.38 (s, 3H), 3.17 (s, 2H), 3.22-3.24 (m, 1H), 3.46 (br. s., 2H), 3.63 (s, 2H), 7.51 (d, J=7.77 Hz, 1H), 7.57-7.73 (m, 5H), 7.86-7.94 (m, 2H), and 12.33 (br. s., 1H).

Provenance & Evidence