Example 14b: Synthesis of 1-(4-fluorobenzoyl)-3-(((6-methoxynaphthalen-2-yl)oxy)methyl)azetidine-3-carboxylic acid
1-(4-Fluorobenzoyl)-3-(((6-methoxy-2-naphthalenyl)oxy)methyl)azetidine-3-carboxylic acid ester (50.0 g, 111.4 mmol, Preparation 33) was suspended in acetonitrile (500 mL), followed by addition of sodium trimethylsilanolate (14.1 g, 126 mmol) and water (2.05 mL, 114 mmol). The suspension was stirred at room temperature for 4 hours. Then, 10% (v/v) aqueous phosphoric acid (100 mL, 171 mmol) was added and the reaction mixture was continued to be stirred at room temperature for 1 h, followed by stirring at 0 °C for 2 h. The reaction mixture was then stirred for 2 h at room temperature. The precipitate was collected, washed twice with water (2 x 250 mL) and dried under reduced pressure to afford the target compound 1-(4-fluorobenzoyl)-3-(((6-methoxynaphthalen-2-yl)oxy)methyl)azetidine-3-carboxylic acid as a white solid in 85% yield (39.5 g).
1H NMR (400 MHz, CD3OD) δ: 3.84 (s, 3H), 4.27 (d, 1H), 4.42 (m, 2H), 4.44 (s, 2H), 4.67 (d, 1H), 7.07 (m, 2H), 7.20 (m, 4H), 7.63 (m, 2H), 7.72 (m, 2H); ES m/z 410 [M + H]+.
![3-Azetidinecarboxylic acid, 1-(4-fluorobenzoyl)-3-[[(6-methoxy-2-naphthalenyl)oxy]methyl]-, ethyl ester](/CAS/20210305/GIF/1078166-69-4.gif)
