Sodium Acetate → 1-[(2-Ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-3-yl}phenyl)methyl]-3-azetidinecarboxylic acid

Participants

Reaction Steps

To a solution of 2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-3-yl}benzaldehyde (D47) (100 mg) in dichloromethane (DCM) (5 mL) and methanol (5.00 mL) was added sodium acetate (39.0 mg) and hydrogen chloride-methyl 3-azetidinecarboxylate (1:1) (72.1 mg). The reaction solution was stirred at room temperature for overnight. Sodium triacetoxyborohydride (101 mg) was added and the resulting solution was stirred at ambient temperature for 2 h. The solvent was removed in vacuo and the residue was dissolved in isopropanol/water (1:1, 5 mL), sodium hydroxide (2.378 mL) was added and the resulting solution was heated to 90° C. for 2 h. Isopropanol was removed in vacuo and the residue was acidified to pH=3-4, extracted with ethyl acetate (2*20 mL), the combined organic phases were dried over sodium sulphate and concentrated, the residue was purified by Mass Directed AutoPrep to afford 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-3-yl}phenyl)methyl]-3-azetidinecarboxylic acid (E19) (44 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.06 (3H, t), 1.27 (6H, d), 2.87 (2H, q), 3.16 (4H, m), 3.34 (1H, m), 3.60 (2H, s), 4.89 (1H, m), 7.23 (1H, t), 7.38 (1H, dd), 7.45 (1H, d), 7.65 (1H, dd), 8.18 (1H, d), 8.25 (1H, dd). δF (DMSO-d6, 376 MHz): −61.4. MS (ES): C26H26F3N3O3S requires 505. found 506.1 (M+H+).

Provenance & Evidence