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

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylbenzaldehyde (D53) (100 mg) in dichloromethane (DCM) (8 mL) and methanol (8.00 mL) was added sodium acetate (31.8 mg), hydrogen chloride-methyl 3-azetidinecarboxylate (1:1) (58.8 mg) and 5 drops of acetic acid. After stirring for 30 min, sodium triacetoxyborohydride (110 mg) was added and the reaction solution was stirred at room temperature overnight. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (30 mL), the organic phase was washed with water, dried over sodium sulphate and concentrated. The residue was dissolved in isopropanol/water (10 mL, 1:1), 0.5M sodium hydroxide (2.58 mL) was added, the reaction solution was heated to 80° C. for 1 h. The solvent was removed in vacuo and the residue was acidified to pH=2-3. The resulting solution was extracted with ethyl acetate (2*15 mL), and the combined organic phases were dried over sodium sulphate, concentrated and purified by Mass Directed AutoPrep to afford 1-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylic acid (E25) (40 mg) as a TFA salt (white solid). δH (DMSO-d6, 400 MHz): 1.05 (3H, t), 1.28 (6H, d), 2.87 (2H, q), 3.19 (3H, m), 3.34 (2H, m), 3.60 (2H, s), 4.78 (1H, m), 7.23 (1H, t), 7.31 (1H, d), 7.38 (1H, d), 7.64 (1H, d), 7.94 (1H, dd), 8.07 (1H, d). δF (DMSO-d6, 376 MHz): −73.4. MS (ES): C24H26ClN3O3S requires 471. found 472.2 (M+H+).

Provenance & Evidence