3-azetidinecarboxylic Acid → HCID 67170150, compound

Participants

Reaction Steps

To a stirring solution of 2-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[2,1-d]thiazole-7-carbaldehyde (0.106 g, 0.249 mmol) in 1,2-dichloroethane (2.0 ml) at room temperature, was added azetidine-3-carboxylic acid (0.075 g, 0.746 mmol). The resulting pale suspension was stirred for 15 min after which tetraisopropyl titanate (0.222 ml, 0.746 mmol) was added dropwise. The reaction mixture turned light orange. Stirring was continued for 4 h after which sodium cyanoborohydride (0.023 g, 0.373 mmol) was added in one portion. After 90 min, the reaction mixture was diluted with MeOH and filtered through Celite. The filter cake was washed with MeOH (2×), and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography (24 g Redisep® cartridge, eluting with 5%-MeOH in dichloromethane followed by 10% (10%-Ammonia-MeOH in dichloromethane) to yield 57 mg of the desired 1-((2-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)methyl)azetidine-3-carboxylic acid as an off white solid. The product had an LC ret. time=1.927 min. (condition: Start % B=0; Final % B=100; Gradient Time=2 min; Flow Rate=5 ml/min; Wavelength=254; Solvent Pair=MeOH/H2O/TFA; Solvent A=0.1% TFA in MeOH: H2O (10:90); Solvent B=0.1% TFA in; MeOH: H2O (10:90); Column 1=Waters Sunfire C18 5 um 4.6×30 mm); LC/MS M+1=512.08. 1H NMR (400 MHz, CD3OD) δ ppm 7.75 (2H, d, J=7.48 Hz), 7.59-7.68 (3H, m), 7.53 (1H, d, J=7.70 Hz), 7.43 (1H, s), 7.38 (1H, dd, J=7.92, 1.54 Hz), 4.34 (2H, s), 4.16-4.23 (4H, m), 3.42 (1H, quin, J=8.36 Hz), 3.12-3.23 (4H, m).

Provenance & Evidence